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Abstract Background Nuts consumption is related to cardioprotective effects on primary cardiovascular prevention, but studies conducted in secondary prevention are small, scarce and controversial. The objective of this trial was to evaluate the effects of a regional and sustainable cardioprotective diet added or not with an affordable mixed nuts on cardiometabolic features in patients with previous myocardial infarction. Methods DICA-NUTS study is a national, multi-center, and superiority-parallel randomized clinical trial. Males and females over 40 years old diagnosed with previous myocardial infarction in the last 2 to 6 months were included. Patients were allocated into two groups: the Brazilian Cardioprotective diet (DICA Br) supplemented with 30 g/day of mixed nuts (10 g of peanuts; 10 g of cashew; 10 g of Brazil nuts) (intervention group, n = 193); or only DICA Br prescription (control group, n = 195). The primary outcome was low-density lipoprotein cholesterol means (in mg/dL) after 16 weeks. Secondary outcomes were other lipid biomarkers, glycemic and anthropometric data and diet quality. Results After adjustment for baseline values, participating study site, time since myocardial infarction and statin treatment regimen (high potency, moderate and low potency/no statins), no significant difference was found between the groups in low-density lipoprotein cholesterol concentrations (intervention-control difference: 3.48 mg/dL [-3.45 to 10.41], P = 0.32). Both groups improved their overall diet quality at the end of the study without differences between them after 16 weeks (intervention-control difference: 1.05 (-0.9 to 2.99); P = 0.29). Other lipids, glycemic profile and anthropometrics were also not different between study groups at the end of the study. Conclusion Adding 30 g/day of mixed nuts to the DICA Br for 16 weeks did not change lipid, glycemic and anthropometric features in the post-myocardial infarction setting. Trial registration This study is registered on ClinicalTrials.gov website under number NCT03728127 and its World Health Organization Universal Trial Number (WHO-UTN) is U1111-1259–8105.

Abstract Background Ceramides have recently been identified as novel biomarkers associated with diabetes mellitus (DM) and major adverse cardiac and cerebrovascular events (MACCE). This study aims to explore their utility in diagnosing microvascular disease. Methods This study prospectively enrolled 309 patients from 2018 to 2020 into three groups: healthy controls (Group 1, N = 51), DM patients without acute myocardial infarction (AMI) (Group 2, N = 150), and DM patients with AMI (Group 3, N = 108). We assessed outcomes using stress perfusion cardiac magnetic resonance (CMR) imaging for coronary microvascular disease (CMD) (Outcome 1), retinography for retinal microvascular disease (RMD) (Outcome 2), both CMD and RMD (Outcome 3), and absence of microvascular disease (w/o MD) (outcome 4). We evaluated the classification performance of ceramides using receiver operating characteristic (ROC) analysis and multiple logistic regression. 11-ceramide panel previously identified by our research group as related to macrovascular disease were used. Results Average glycated hemoglobin (HbA1c) values were 5.1% in Group 1, 8.3% in Group 2, and 7.6% in Group 3. Within the cohort, CMD was present in 59.5% of patients, RMD in 25.8%, both CMD and RMD in 18.8%, and w/o MD in 38.5%. The AUC values for the reference ceramide ratios were as follows: CMD at 0.66 (p = 0.012), RMD at 0.61 (p = 0.248), CMD & RMD at 0.64 (p = 0.282), and w/o MD at 0.67 (p = 0.010). In contrast, the AUC values using 11-ceramide panel showed significant improvement in the outcomes prediction: CMD at 0.81 (p = 0.001), RMD at 0.73 (p = 0.010), CMD & RMD at 0.73 (p = 0.04), and w/o MD at 0.83 (p = 0.010). Additionally, the plasma concentration of C14.0 was notably higher in the w/o MD group (p

Summary: Background and aims: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. Methods: A national, multicenter, factorial, and parallel placebo-controlled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICA-FH) + phytosterol placebo + krill oil placebo; 2) DICA-FH + phytosterol 2 g/day + krill oil placebo; 3) DICA-FH + phytosterol placebo + krill oil 2 g/day; or 4) DICA-FH + phytosterol 2 g/day + krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. Results: A total of 58 participants were enrolled between May–August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. Conclusions: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

IntroductionInfections acquired during healthcare setting stay pose significant public health threats. These infections are known as Healthcare-Associated Infections (HAI), mostly caused by pathogenic bacteria, which exhibit a wide range of antimicrobial resistance. Currently, there is no knowledge about the global cleaning process of hospitals and the bacterial diversity found in ICUs of Brazilian hospitals contributing to HAI.ObjectiveCharacterize the microbiome and common antimicrobial resistance genes present in high-touch Intensive Care Unit (ICU) surfaces, and to identify the potential contamination of the sanitizers/processes used to clean hospital surfaces.MethodsIn this national, multicenter, observational, and prospective cohort, bacterial profiles and several antimicrobial resistance genes from 41 hospitals across 16 Brazilian states were evaluated. Using high-throughput 16S rRNA amplicon sequencing and real-time PCR, the bacterial abundance and resistance genes presence were analyzed in both ICU environments and cleaning products.ResultsWe identified a wide diversity of microbial populations with a recurring presence of HAI-related bacteria among most of the hospitals. The median bacterial positivity rate in surface samples was high (88.24%), varying from 21.62 to 100% in different hospitals. Hospitals with the highest bacterial load in samples were also the ones with highest HAI-related abundances. Streptococcus spp., Corynebacterium spp., Staphylococcus spp., Bacillus spp., Acinetobacter spp., and bacteria from the Flavobacteriaceae family were the microorganisms most found across all hospitals. Despite each hospital particularities in bacterial composition, clustering profiles were found for surfaces and locations in the ICU. Antimicrobial resistance genes mecA, blaKPC-like, blaNDM-like, and blaOXA-23-like were the most frequently detected in surface samples. A wide variety of sanitizers were collected, with 19 different active principles in-use, and 21% of the solutions collected showed viable bacterial growth with antimicrobial resistance genes detected.ConclusionThis study demonstrated a diverse and spread pattern of bacteria and antimicrobial resistance genes covering a large part of the national territory in ICU surface samples and in sanitizers solutions. This data should contribute to the adoption of surveillance programs to improve HAI control strategies and demonstrate that large-scale epidemiology studies must be performed to further understand the implications of bacterial contamination in hospital surfaces and sanitizer solutions.

Objectives Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.Design Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.Eligibility criteria Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.Data synthesis The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I2 evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.Results A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI −4.00 to 9.88, I2=79.3%; %DLco −2.03, 95% CI −4.38 to 0.32, I2=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I2=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DLCO (95% CI 2.05 to 6.79, I2=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.Conclusions There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.PROSPERO registration number CRD42023423223.

Abstract Introduction Shorter courses of antimicrobials have been shown to be non-inferior to longer, “traditional” duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB. Methods This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days. Planned Outcomes The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%. Conclusion The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB. Trial Registration ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE).

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Central nervous system (CNS) malignant neoplasms may lead to venous thromboembolism (VTE) and bleeding, which result in rehospitalization, morbidity and mortality. We aimed to assess the incidence of VTE and bleeding in this population.MethodsThis systematic review and meta-analysis (PROSPERO CRD42023423949) were based on a standardized search of PubMed, Virtual Health Library and Cochrane (n = 1653) in July 2023. After duplicate removal, data screening and collection were conducted by independent reviewers. The combined rates and 95% confidence intervals for the incidence of VTE and bleeding were calculated using the random effects model with double arcsine transformation. Subgroup analyses were performed based on sex, age, income, and type of tumor. Heterogeneity was calculated using Cochran's Q test and I2 statistics. Egger's test and funnel graphs were used to assess publication bias.ResultsOnly 36 studies were included, mainly retrospective cohorts (n = 30, 83.3%) from North America (n = 20). Most studies included were published in high-income countries. The sample size of studies varied between 34 and 21,384 adult patients, mostly based on gliomas (n = 30,045). For overall malignant primary CNS neoplasm, the pooled incidence was 13.68% (95%CI 9.79; 18.79) and 11.60% (95%CI 6.16; 18.41) for VTE and bleeding, respectively. The subgroup with elderly people aged 60 or over had the highest incidence of VTE (32.27% - 95%CI 14.40;53.31). The studies presented few biases, being mostly high quality. Despite some variability among the studies, we observed consistent results by performing sensitivity analysis, which highlight the robustness of our findings.ConclusionsOur study showed variability in the pooled incidence for both overall events and subgroup analyses. It was highlighted that individuals over 60 years old or diagnosed with GBM had a higher pooled incidence of VTE among those with overall CNS malignancies. It is important to note that the results of this meta-analysis refer mainly to studies carried out in high-income countries. This highlights the need for additional research in Latin America, and low- and middle-income countries.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.

Objectives: The objective of this study was to evaluate the effect of intercessory prayer performed by a group of spiritual leaders on the health outcomes of hospitalized patients with Novel Coronavirus (COVID-19) infection, specifically focusing on mortality and hospitalization rates. Design: This was a double-blinded, controlled, and randomized trial conducted at a private hospital in São Paulo, Brazil. Interventions: Both groups continued to receive their usual medical care in accordance with HCor Hospital's institutional patient care protocol for COVID-19 patients. Intervention: Both groups received their regular medical care according to HCor's institutional patient care protocol for COVID-19 patients. The intervention group, in addition to standard treatment, received intercessory prayers performed by a group of spiritual leaders. Main outcome measures: The primary endpoint was in-hospital mortality. Secondary endpoints included the need for mechanical ventilation during hospitalization, duration of mechanical ventilation, length of ICU stay, and length of hospital stay. Results: A total of 199 participants were randomly assigned to the groups. The primary outcome, in-hospital mortality, occurred in 8 out of 100 (8.0 %) patients in the intercessory prayer group and 8 out of 99 (8.1 %) patients in the control group (HR 0.86 [0.32 to 2.31]; p = 0.76). Additionally, there were no significant differences between the groups in terms of secondary outcomes. Conclusion: The study found no evidence of an effect of intercessory prayer on the primary outcome of mortality or on the secondary outcomes of hospitalization time, ICU time, and mechanical ventilation time.

RESUMO Os medicamentos reaproveitados são importantes em contextos de recursos limitados porque as intervenções estão mais rapidamente disponíveis, já foram testadas com segurança em outras populações e são, em geral, mais baratas. Os medicamentos reaproveitados são uma solução eficaz, especialmente para doenças emergentes, como a COVID-19. O estudo REVOLUTIOn visa avaliar três medicamentos antivirais reaproveitados: atazanavir, daclatasvir e sofosbuvir, já utilizados em pacientes infectados pelo HIV ou pelo vírus da hepatite C, em um estudo randomizado, controlado por placebo, adaptativo, multibraço e em múltiplos estágios. Os medicamentos serão testados simultaneamente em um ensaio de Fase II para primeiro identificar se algum deles, isoladamente ou em combinação, reduz a carga viral. Se reduzirem, será iniciado um estudo de Fase III para investigar se tais medicamentos são capazes de aumentar o número de dias sem suporte respiratório. Os participantes devem ser adultos hospitalizados com idade ≥ 18 anos com início dos sintomas ≤ 9 dias e saturação de oxigênio ≤ 94% em ar ambiente ou necessidade de oxigênio suplementar para manter saturação de oxigênio > 94%. O tamanho total esperado da amostra varia entre 252 e 1.005 participantes, dependendo do número de estágios que serão concluídos no estudo. Assim, o protocolo é aqui descrito em detalhes, juntamente do plano de análise estatística. Em conclusão, o estudo REVOLUTIOn foi concebido para fornecer evidências se o atazanavir, o daclatasvir ou o sofosbuvir reduzem a carga viral de SARS-CoV-2 em pacientes com COVID-19 e aumentam o número de dias em que os pacientes ficam sem suporte respiratório. Neste artigo de protocolo, descrevem-se a fundamentação, o desenho e a situação do ensaio. Identificador do ClinicalTrials.gov:NCT04468087

RESUMO Objetivo: O ensaio TELE-critical Care verSus usual Care On ICU PErformance (TELESCOPE) visa avaliar se uma intervenção complexa por telemedicina em unidades de terapia intensiva, que se concentra em rondas multidisciplinares diárias realizadas por intensivistas a distância, reduzirá o tempo de permanência na unidade de terapia intensiva em comparação com os cuidados habituais. Métodos: O TELESCOPE é um ensaio nacional, multicêntrico, controlado, aberto, randomizado em cluster. O estudo testa a eficácia de rondas multidisciplinares diárias realizadas por um intensivista por meio de telemedicina em unidades de terapia intensiva brasileiras. O protocolo foi aprovado pelo Comitê de Ética em Pesquisa local do centro coordenador do estudo e pelo Comitê de Ética em Pesquisa local de cada uma das 30 unidades de terapia intensiva, de acordo com a legislação brasileira. O ensaio está registado no ClinicalTrials.gov (NCT03920501). O desfecho primário é o tempo de internação na unidade de terapia intensiva, que será analisado considerando o período basal e a estrutura dos dados em cluster, sendo ajustado por covariáveis predefinidas. Os desfechos exploratórios secundários incluem a classificação de desempenho da unidade de terapia intensiva, a mortalidade hospitalar, a incidência de infecções nosocomiais, o número de dias sem ventilação mecânica aos 28 dias, a taxa de pacientes que recebem alimentação oral ou enteral, a taxa de pacientes sob sedação leve ou em alerta e calmos e a taxa de pacientes sob normoxemia. Conclusão: De acordo com as melhores práticas do ensaio, divulgamos nossa análise estatística antes de bloquear a base de dados e iniciar as análises. Esperamos que essa prática de notificação evite o viés das análises e aprimore a interpretação dos resultados apresentados. Registro no ClinicalTrials.gov:NCT03920501

RESUMO Introdução: A reversão precoce da hipoperfusão tecidual induzida é essencial para a sobrevida no choque séptico. No entanto, falta consenso sobre a melhor estratégia de ressuscitação inicial, uma vez que intervenções destinadas a toda a população com choque séptico podem produzir administração desnecessária de líquidos. Este artigo relata a justificativa, o delineamento e o plano de análise do estudo ANDROMEDA-2, que visa determinar se uma estratégia guiada por perfusão periférica, que consiste na ressuscitação guiada pelo tempo de enchimento capilar com base em fenótipos clínicos e hemodinâmicos, está associada a uma diminuição no desfecho composto de mortalidade, tempo até a interrupção ao suporte de órgãos e tempo de internação em comparação com o atendimento padrão em pacientes com choque séptico precoce (< 4 horas do diagnóstico). Metódos: O estudo ANDROMEDA-2 é um ensaio clínico randomizado controlado multinacional e multicêntrico. No grupo de intervenção, o tempo de enchimento capilar será medido a cada hora, durante 6 horas. Se estiver anormal, os pacientes serão alocados em um algoritmo, começando com a avaliação da pressão de pulso. Pacientes com pressão de pulso inferior a 40mmHg serão testados quanto à capacidade de resposta a líquidos e receberão líquidos de acordo. Em pacientes com pressão de pulso > 40mmHg, norepinefrina será titulada para manter a pressão arterial diastólica > 50mmHg. Os pacientes que não normalizarem o tempo de enchimento capilar após as etapas anteriores serão submetidos à ecocardiografia de cuidados intensivos para avaliação da disfunção cardíaca e posterior manejo. Por fim, serão realizados testes com vasopressores e inodilatadores para otimizar ainda mais a perfusão. Um tamanho de amostra de 1.500 pacientes fornecerá 88% de poder para demonstrar a superioridade da estratégia direcionada ao tempo de enchimento capilar. Conclusão: Se for demonstrado que o direcionamento ao tempo de enchimento capilar é uma estratégia melhor, os processos de atendimento na ressuscitação do choque séptico podem ser otimizados com ferramentas usadas à beira do leito.

Resumo Fundamento: Revisões sistemáticas anteriores não identificaram benefício do uso da hidroxicloroquina ou da cloroquina em pacientes com COVID-19 não hospitalizados. Após a publicação dessas revisões, os resultados do COPE, o maior ensaio clínico randomizado até hoje, tornaram-se disponíveis. Objetivos: Conduzir uma revisão sistemática e metanálise de ensaios clínicos randomizados (ECRs) para sintetizar as evidências sobre a eficácia e a segurança da hidroxicloroquina e da cloroquina em pacientes com COVID-19 não hospitalizados em comparação a controle ou tratamento padrão. Métodos: As buscas foram conduzidas nos bancos de dados PubMed, Embase, The Cochrane Library e ClinicalTrials.gov, e complementadas por busca manual. Foram realizadas metanálises diretas e avaliações de risco de viés e certeza da evidência, incluindo análise do tamanho ótimo da informação (OIS, optimal information size). Um nível de significância de 0,05 foi adotado na metanálise. PROSPERO: CRD42021265427. Resultados: Oito ECRs com 3219 participantes foram incluídos. As taxas de internação por COVID-19 e de eventos adversos não foram significativamente diferentes entre hidroxicloroquina (5,6% e 5,1%) e controle (7,4% e 20,4%) [risco relativo (RR) 0,77, intervalo de confiança 95% (IC95%), 0,57-1,04, I2: 0%; RR 1,78, IC95% 0,90; 3,52, I2: 93%, respectivamente)]. O OIS (7880) não foi alcançado para hospitalização por COVID-19, independentemente da simulação para a taxa de evento e redução do RR estimados. Conclusão: A evidência de muito baixa qualidade indicou falta de benefício com hidroxicloroquina em prevenir internações por COVID-19. Apesar de ser a revisão sistemática com o maior número de participantes incluídos, o OIS, considerando a resposta à infecção anterior à vacinação, não foi atingido.

Abstract Background Nut consumption has been related to improvements on cardiometabolic parameters and reduction in the severity of atherosclerosis mainly in primary cardiovascular prevention. The objective of this trial is to evaluate the effects of the Brazilian Cardioprotective Diet (DI eta CA rdioprotetora Br asileira, DICA Br) based on consumption of inexpensive locally accessible foods supplemented or not with mixed nuts on cardiometabolic features in patients with previous myocardial infarction (MI). Methods DICA-NUTS study is a national, multicenter, randomized 16-week follow-up clinical trial. Patients over 40 years old with diagnosis of previous MI in the last 2 to 6 months will be recruited (n = 388). A standardized questionnaire will be applied to data collection and blood samples will be obtained. Patients will be allocated in two groups: Group 1: DICA Br supplemented with 30 g/day of mixed nuts (10 g of peanuts, 10 g of cashew, 10 g of Brazil nuts); and Group 2: only DICA Br. The primary outcome will consist of LDL cholesterol means (in mg/dL) after 16 weeks of intervention. Secondary outcomes will consist of other markers of lipid profile, glycemic profile, and anthropometric data. Discussion It is expected that DICA Br supplemented with mixed nuts have superior beneficial effects on cardiometabolic parameters in patients after a MI, when compared to DICA Br. Trial registration ClinicalTrials.gov Identifier NCT03728127 . First register: November 1, 2018; Last update: June 16, 2021. World Health Organization Universal Trial Number (WHO-UTN): U1111-1259-8105.

ABSTRACT Objective To verify the association between a multiprofessional round with the use of checklists and patient safety practices by health professionals in an intensive care unit. Method Mixed-method study, delineated by the sequential explanatory approach, conducted in a hospital in southern Brazil. Quantitative data were analyzed using Poisson regression, and qualitative data, using content analysis. The integrated analysis was performed through the explained/connected combination. Results In the post-implementation period of the rounds with systematic use of the checklist, there was a significant improvement in the prophylaxis of venous thromboembolism, light sedation, reduction in the days of use of mechanical ventilation, central venous catheter and indwelling urinary catheter. Conclusion The multiprofessional round with the systematic use of checklist, associated with the improvement in patient safety practices, was considered as a strategy that ensures better care in intensive care and favors job satisfaction.

ABSTRACT Objectives: to analyze the implementation of multidisciplinary checklist-directed rounds before health indicators and multidisciplinary team perception of an Intensive Care Unit. Methods: a mixed methods study, with an explanatory sequential design, carried out at a hospital in southern Brazil, from September 2020 to August 2021. The integration of quantitative and qualitative data was combined by connection. Results: after the implementation of checklist-directed rounds, there was a significant reduction in hospital stay from ventilator-associated pneumonia, urinary tract infection and daily invasive device use. The investigated practice is essential for comprehensive care, harm reduction, effective work and critical patient safety. Conclusions: the multidisciplinary rounds with checklist use reduced data on health indicators of critically ill patients and was considered a vital practice in the intensive care setting.

RESUMO Objetivo: Descrever as práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras e compará-las com as de outros países participantes do estudo Fluid-TRIPS. Métodos: Este foi um estudo observacional transversal, prospectivo e internacional, de uma amostra de conveniência de unidades de terapia intensiva de 27 países (inclusive o Brasil), com utilização da base de dados Fluid-TRIPS compilada em 2014. Descrevemos os padrões de ressuscitação volêmica utilizados no Brasil em comparação com os de outros países e identificamos os fatores associados com a escolha dos fluidos. Resultados: No dia do estudo, foram incluídos 3.214 pacientes do Brasil e 3.493 pacientes de outros países, dos quais, respectivamente, 16,1% e 26,8% (p < 0,001) receberam fluidos. A principal indicação para ressuscitação volêmica foi comprometimento da perfusão e/ou baixo débito cardíaco (Brasil 71,7% versus outros países 56,4%; p < 0,001). No Brasil, a percentagem de pacientes que receberam soluções cristaloides foi mais elevada (97,7% versus 76,8%; p < 0,001), e solução de cloreto de sódio a 0,9% foi o cristaloide mais comumente utilizado (62,5% versus 27,1%; p < 0,001). A análise multivariada sugeriu que os níveis de albumina se associaram com o uso tanto de cristaloides quanto de coloides, enquanto o tipo de prescritor dos fluidos se associou apenas com o uso de cristaloides. Conclusão: Nossos resultados sugerem que cristaloides são usados mais frequentemente do que coloides para ressuscitação no Brasil, e essa discrepância, em termos de frequências, é mais elevada do que em outros países. A solução de cloreto de sódio 0,9% foi o cristaloide mais frequentemente prescrito. Os níveis de albumina sérica e o tipo de prescritor de fluidos foram os fatores associados com a escolha de cristaloides ou coloides para a prescrição de fluidos.

Abstract Objective To contribute to updating the recommendations for brain-dead potential organ donor management. Method A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, joined a task force formed by the General Coordination Office of the National Transplant System/Brazilian Ministry of Health (CGSNT-MS), the Brazilian Association of Intensive Care Medicine (AMIB), the Brazilian Association of Organ Transplantation (ABTO), and the Brazilian Research in Intensive Care Network (BRICNet). The questions were developed within the scope of the 2011 Brazilian Guidelines for Management of Adult Potential Multiple-Organ Deceased Donors. The topics were divided into mechanical ventilation, hemodynamic support, endocrine-metabolic management, infection, body temperature, blood transfusion, and use of checklists. The outcomes considered for decision-making were cardiac arrest, number of organs recovered or transplanted per donor, and graft function/survival. Rapid systematic reviews were conducted, and the quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Two expert panels were held in November 2016 and February 2017 to classify the recommendations. A systematic review update was performed in June 2020, and the recommendations were reviewed through a Delphi process with the panelists between June and July 2020. Results A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong (lung-protective ventilation strategy, vasopressors and combining arginine vasopressin to control blood pressure, antidiuretic hormones to control polyuria, serum potassium and magnesium control, and antibiotic use), 11 as weak (alveolar recruitment maneuvers, low-dose dopamine, low-dose corticosteroids, thyroid hormones, glycemic and serum sodium control, nutritional support, body temperature control or hypothermia, red blood cell transfusion, and goal-directed protocols), and 1 was considered a good clinical practice (volemic expansion). Conclusion Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak. The observed lack of robust evidence on the topic highlights the importance of the present guideline to improve the management of brain-dead potential organ donors.

RESUMO A pandemia por COVID-19 tem deixado os gestores, os profissionais de saúde e a população preocupados com a potencial escassez de ventiladores pulmonares para suporte de pacientes graves. No Brasil, há diversas iniciativas com o intuito de produzir ventiladores alternativos para ajudar a suprir essa demanda. Para auxiliar as equipes que atuam nessas iniciativas, são expostos alguns conceitos básicos sobre fisiologia e mecânica respiratória, os termos comumente utilizados no contexto da ventilação mecânica, as fases do ciclo ventilatório, as diferenças entre disparo e ciclagem, os modos ventilatórios básicos e outros aspectos relevantes, como mecanismos de lesão pulmonar induzida pela ventilação mecânica, pacientes com drive respiratório, necessidade de umidificação de vias aéreas, risco de contaminação cruzada e disseminação de aerossóis. Após a fase de desenvolvimento de protótipo, são necessários testes pré-clínicos de bancada e em modelos animais, a fim de determinar a segurança e o desempenho dos equipamentos, seguindo requisitos técnicos mínimos exigidos. Então, é imprescindível passar pelo processo regulatório exigido pela Agência Nacional de Vigilância Sanitária (ANVISA). A empresa responsável pela fabricação do equipamento deve estar regularizada junto à ANVISA, que também deve ser notificada da condução dos testes clínicos em humanos, seguindo protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. O registro do ventilador junto à ANVISA deve ser acompanhado de um dossiê, composto por documentos e informações detalhadas neste artigo, que não tem o propósito de esgotar o assunto, mas de nortear os procedimentos necessários.

Abstract Background Survival benefit from low tidal volume (V T) ventilation (LTVV) has been demonstrated for patients with acute respiratory distress syndrome (ARDS), and patients not having ARDS could also benefit from this strategy. Organizational factors may play a role on adherence to LTVV. The present study aimed to identify organizational factors with an independent association with adherence to LTVV. Methods Secondary analysis of the database of a multicenter two-phase study (prospective cohort followed by a cluster-randomized trial) performed in 118 Brazilian intensive care units. Patients under mechanical ventilation at day 2 were included. LTVV was defined as a V T ≤ 8 ml/kg PBW on the second day of ventilation. Data on the type and number of beds of the hospital, teaching status, nursing, respiratory therapists and physician staffing, use of structured checklist, and presence of protocols were tested. A multivariable mixed-effect model was used to assess the association between organizational factors and adherence to LTVV. Results The study included 5719 patients; 3340 (58%) patients received LTVV. A greater number of hospital beds (absolute difference 7.43% [95% confidence interval 0.61–14.24%]; p = 0.038), use of structured checklist during multidisciplinary rounds (5.10% [0.55–9.81%]; p = 0.030), and presence of at least one nurse per 10 patients during all shifts (17.24% [0.85–33.60%]; p = 0.045) were the only three factors that had an independent association with adherence to LTVV. Conclusions Number of hospital beds, use of a structured checklist during multidisciplinary rounds, and nurse staffing are organizational factors associated with adherence to LTVV. These findings shed light on organizational factors that may improve ventilation in critically ill patients.

Abstract Background The quality of clinical care of brain-dead potential organ donors may help reduce donor losses caused by irreversible or unreversed cardiac arrest and increase the number of organs donated. We sought to determine whether an evidence-based, goal-directed checklist for donor management in intensive care units (ICUs) can reduce donor losses to cardiac arrest. Methods/design The DONORS study is a multicentre, cluster-randomised controlled trial with a 1:1 allocation ratio designed to compare an intervention group (goal-directed checklist for brain-dead potential organ donor management) with a control group (standard ICU care). The primary outcome is loss of potential donors due to cardiac arrest. Secondary outcomes are the number of actual organ donors and the number of solid organs recovered per actual donor. Exploratory outcomes include the achievement of relevant clinical goals during the management of brain-dead potential organ donors. The present statistical analysis plan (SAP) describes all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of the trial. Discussion The SAP of the DONORS study aims to describe its analytic procedures, enhancing the transparency of the study. At the moment of SAP subsmission, 63 institutions have been randomised and were enrolling study participants. Thus, the analyses reported herein have been defined before the end of the study recruitment and database locking. Trial registration ClinicalTrials.gov, NCT03179020 . Registered on 7 June 2017.

Abstract Objective: To analyze the profile and outcomes of patients who underwent valve heart surgery in Brazil, using information retrieved from the Brazilian Registry of Cardiovascular Surgeries in Adults (BYPASS Registry) database. Methods: This is a multicenter cohort study, evaluating 920 patients submitted to heart valve surgery. Demographics and postoperative clinical outcomes were assessed and compared to estimate mortality risk using the European System for Cardiac Operative Risk Evaluation (EuroSCORE). Results: Isolated aortic valve replacement was the most frequently performed surgery (34%), followed by isolated mitral valve replacement (24.9%). Valve repair was performed in 21% of mitral procedures. Minimally invasive access was performed in 1.6% and the most frequent postoperative complications were arrhythmias (22.6%), infections (5.7%), and low-output syndrome (5.1%). Operations covered by the public health system accounted for 80.8% and the hospital mortality rate was 7.3%. Conclusion: The most frequent isolated valve surgery in Brazil is the aortic valve replacement by conventional open access and the rheumatic disease is still the main etiology for valve surgery. The BYPASS Registry has a fundamental role to provide information on the profile of patients with valve heart disease in our country in order to delineate adequate strategies for health promotion and resource allocation for cardiac surgery.

Abstract Background Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock. Methods A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. Results Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0–510] vs. 1500[650–2300] mL, p

OBJECTIVE: To evaluate the clinical effects of early administration of fibrinogen concentrate in patients with severe trauma and hypofibrinogenemia. METHODS: We conducted an open randomized feasibility trial between December 2015 and January 2017 in patients with severe trauma admitted to the emergency department of a large trauma center. Patients presented with hypotension, tachycardia, and FIBTEM findings suggestive of hypofibrinogenemia. The intervention group received fibrinogen concentrate (50 mg/kg), and the control group did not receive early fibrinogen replacement. The primary outcome was feasibility assessed as the proportion of patients receiving the allocated treatment within 60 min after randomization. The secondary outcomes were transfusion requirements and other exploratory outcomes. Randomization was performed using sequentially numbered and sealed opaque envelopes. ClinicalTrials.gov: NCT02864875. RESULTS: Thirty-two patients were randomized (16 in each group). All patients received the allocated treatment within 60 min after randomization (100%, 95% confidence interval, 86.7%-100%). The median length of intensive care unit stay was shorter in the intervention group (8 days, interquartile range [IQR] 5.75-10.0 vs. 11 days, IQR 8.5-16.0; p=0.02). There was no difference between the groups in other clinical outcomes. No adverse effects related to treatment were recorded in either group. CONCLUSION: Early fibrinogen replacement with fibrinogen concentrate was feasible. Larger trials are required to properly evaluate clinical outcomes.

Introduction Daily multidisciplinary rounds (DMRs) consist of systematic patient-centred discussions aiming to establish joint therapeutic goals for the next 24 hours of intensive care unit (ICU) care. The aim of the present study protocol is to evaluate whether an intervention consisting of guided DMRs, supported by a remote specialist and audit/feedback on care performance will reduce ICU length of stay compared with a control group.Methods and analysis A multicentre, controlled, cluster-randomised superiority trial including 30 ICUs in Brazil (15 intervention and 15 control), from August 2019 to June 2021. In a parallel assignment, ICUs are randomised to a complex-intervention composed by daily rounds carried out through Tele-ICU by a remote ICU physician; development of local quality indicators dashboards coupled with monthly meetings with local leadership; and dissemination of evidence-based clinical protocols versus usual care. Primary outcome is ICU length of stay. Secondary outcomes include classification of the unit according to the profiles defined by the standardised resource use and the standardised mortality rate, hospital mortality, incidence of healthcare-associated infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation or alert and calm, rate of patients under normoxaemia. All adult patients admitted after the beginning of the study in each participant ICU will be enrolled. Inclusion criteria (clusters): public Brazilian ICUs with a minimum of 8 ICU beds interested/committed to participating in the study. Exclusion criteria (clusters): units with fully established DMRs by an intensivist, specialised or step-down units.Ethics and dissemination The study protocol was approved by the institutional review board (IRB) of the coordinator centre, and by IRBs of each enrolled hospital/ICU. Statistical analysis protocol is being prepared for submission before the end of patient’s enrolment. Results will be disseminated through conferences, peer-reviewed journals and to each participating unit.Trial registration number NCT03920501; Pre-results.

Abstract Background Although light sedation levels are associated with several beneficial outcomes for critically ill patients on mechanical ventilation, the majority of patients are still deeply sedated. Organizational factors may play a role on adherence to light sedation levels. We aimed to identify organizational factors associated with a moderate to light sedation target on the first 48 h of mechanical ventilation, as well as the association between early achievement of within-target sedation and mortality. Methods This study is a secondary analysis of a multicenter two-phase study (prospective cohort followed by a cluster-randomized controlled trial) performed in 118 Brazilian ICUs. We included all critically ill patients who were on mechanical ventilation 48 h after ICU admission. A moderate to light level of sedation or being alert and calm (i.e., the Richmond Agitation-Sedation Scale of − 3 to 0) was the target for all patients on mechanical ventilation during the study period. We collected data on the type of hospital (public, private, profit and private, nonprofit), hospital teaching status, nursing and physician staffing, and presence of sedation, analgesia, and weaning protocols. We used multivariate random-effects regression with ICU and study phase as random-effects and correction for patients’ Simplified Acute Physiology Score 3 and Sequential Organ Failure Assessment. We also performed a mediation analysis to explore whether sedation level was just a mediator of the association between organizational factors and mortality. Results We included 5719 patients. Only 1710 (29.9%) were on target sedation levels on day 2. Board-certified intensivists on the morning and afternoon shifts were associated with an adequate sedation level on day 2 (OR = 2.43; CI 95%, 1.09–5.38). Target sedation levels were associated with reduced hospital mortality (OR = 0.63; CI 95%, 0.55–0.72). Mediation analysis also suggested such an association, but did not suggest a relationship between the physician staffing model and hospital mortality. Conclusions Board-certified intensivists on morning and afternoon shifts were associated with an increased number of patients achieving lighter sedation goals. These findings reinforce the importance of organizational factors, such as intensivists’ presence, as a modifiable quality improvement target.

Abstract Background Most adult intensive care units (ICUs) worldwide adopt restrictive family visitation models (RFVMs). However, evidence, mostly from non-randomized studies, suggests that flexible adult ICU visiting hours are safe policies that can result in benefits such as prevention of delirium and increase in satisfaction with care. Accordingly, the ICU Visits Study was designed to compare the effectiveness and safety of a flexible family visitation model (FFVM) vs. an RFVM on delirium prevention among ICU patients, and also to analyze its potential effects on family members and ICU professionals. Methods/design The ICU Visits Study is a cluster-randomized crossover trial which compares an FFVM (12 consecutive ICU visiting hours per day) with an RFVM (

RESUMO Fundamentação: O estudo ANDROMEDA-SHOCK é um estudo internacional, multicêntrico, randomizado e controlado comparando ressuscitação guiada pela perfusão periférica com ressuscitação guiada pelo lactato em pacientes com choque séptico, com a finalidade de testar a hipótese de que a ressuscitação guiada pela perfusão periférica associa-se a menor morbidade e mortalidade. Objetivo: Relatar o plano de análise estatística para o estudo ANDROMEDA-SHOCK. Métodos: Descrevemos o delineamento do estudo, os objetivos primário e secundários, pacientes, métodos de randomização, intervenções, desfechos e tamanho da amostra. Descrevemos nossos planos de análise estatística para os desfechos primários, secundários e terciários. Também descrevemos as análises de subgrupos e sensibilidade. Finalmente, fornecemos detalhes para a apresentação dos resultados, inclusive modelos de tabelas para apresentar as características basais, a evolução das variáveis de hemodinâmica e perfusão, e os efeitos dos tratamentos nos desfechos. Conclusão: Segundo as melhores práticas de pesquisa, relatamos nosso plano de análise estatística e plano de gestão de dados antes do fechamento da base de dados e do início da análise dos dados. Nossa expectativa é que este procedimento previna a ocorrência de vieses na análise e incremente a utilidade dos resultados relatados.

Abstract Background Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to increases in flow that could lead to a more timely decision to stop resuscitation, thus avoiding fluid overload and the risks of over-resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA-SHOCK Study. Methods ANDROMEDA-SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion-targeted resuscitation is associated with lower 28-day mortality compared to a lactate-targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8-hour study period pursuing normalization of capillary refill time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with fluid responsiveness assessment and fluid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28-day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the first 28 days after randomization; multiple organ dysfunction during the first 72 h after randomization; intensive care unit and hospital lengths of stay; and all-cause mortality at 90-day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Conclusions If peripheral perfusion-targeted resuscitation improves 28-day mortality, this could lead to simplified algorithms, assessing almost in real-time the reperfusion process, and pursuing more physiologically sound objectives. At the end, it might prevent the risk of over-resuscitation and lead to a better utilization of intensive care unit resources. Trial registration ClinicalTrials.gov Identifier: NCT03078712 (registered retrospectively March 13th, 2017)

Abstract Background Intensive care medicine is a relatively young discipline that has rapidly grown into a full-fledged medical subspecialty. Intensivists are responsible for managing an ever-increasing number of patients with complex, life-threatening diseases. Several factors may influence their performance, including age, training, experience, workload, and socioeconomic context. The aim of this study was to examine individual- and work-related aspects of the Latin American intensivist workforce, mainly with academic appointments, which might influence the quality of care provided. In consequence, we conducted a cross-sectional study of intensivists at public and private academic and nonacademic Latin American intensive care units (ICUs) through a web-based electronic survey submitted by email. Questions about personal aspects, work-related topics, and general clinical workflow were incorporated. Results Our study comprised 735 survey respondents (53% return rate) with the following country-specific breakdown: Brazil (29%); Argentina (19%); Chile (17%); Uruguay (12%); Ecuador (9%); Mexico (7%); Colombia (5%); and Bolivia, Peru, Guatemala, and Paraguay combined (2%). Latin American intensivists were predominantly male (68%) young adults (median age, 40 [IQR, 35–48] years) with a median clinical ICU experience of 10 (IQR, 5–20) years. The median weekly workload was 60 (IQR, 47–70) h. ICU formal training was between 2 and 4 years. Only 63% of academic ICUs performed multidisciplinary rounds. Most intensivists (85%) reported adequate conditions to manage patients with septic shock in their units. Unsatisfactory conditions were attributed to insufficient technology (11%), laboratory support (5%), imaging resources (5%), and drug shortages (5%). Seventy percent of intensivists participated in research, and 54% read scientific studies regularly, whereas 32% read no more than one scientific study per month. Research grants and pharmaceutical sponsorship are unusual funding sources in Latin America. Although Latin American intensivists are mostly unsatisfied with their income (81%), only a minority (27%) considered changing to another specialty before retirement. Conclusions Latin American intensivists constitute a predominantly young adult workforce, mostly formally trained, have a high workload, and most are interested in research. They are under important limitations owing to resource constraints and overt dissatisfaction. Latin America may be representative of other world areas with similar challenges for intensivists. Specific initiatives aimed at addressing these situations need to be devised to improve the quality of critical care delivery in Latin America.

Abstract Background Preliminary evidence suggests statins may reduce major perioperative vascular events. However, evidence is limited to observational studies, underpowered trials, and non-comprehensive systematic reviews. This review aims to assess the effects of perioperative statin use on cardiovascular complications in patients submitted to non-cardiac surgery. Methods We will search MEDLINE/PubMed, EMBASE, LILACS, CENTRAL, Web of Science, and CINAHL for randomized controlled trials assessing the effects of perioperative statin use in adults undergoing non-cardiac surgery and reporting cardiovascular complications. For patients already using statins for hyperlipidemia, a preoperative loading dose of statin is required in the experimental group. We will place no language or publication restriction on our search. Teams of two reviewers will independently assess eligibility and risk of bias, and will extract data from the included trials. Our primary outcome is a combination of cardiovascular mortality or non-fatal myocardial infarction. We will also assess the following outcomes: individual components of the primary outcome, all-cause mortality, total myocardial infarction, elevated troponin in the first seven postoperative days, total stroke, total venous thromboembolism, postoperative atrial fibrillation, elevation of creatine phosphokinase or liver enzymes, and rates of myalgia or rhabdomyolysis. We will conduct meta-analyses using random-effects model and will use trial sequential analysis to establish monitoring boundaries to limit global type I error due to repetitive testing for our primary outcome. We will rate the quality of evidence using the GRADE system. Discussion The results of this systematic review may help to inform clinical practice and also the design of future large-scale randomized trials. Systematic review registration PROSPERO CRD42016035987

Abstract Background: The choice of a mechanical (MP) or biological prosthesis (BP) for patients with valvular heart disease undergoing replacement is still not a consensus. Objective: We aimed to determine the clinical outcomes of MP or BP placement in those patients. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared biological prostheses and mechanical prostheses in patients with valvular heart diseases and assessed the outcomes. RCTs were searched in the MEDLINE, EMBASE, LILACS, CENTRAL, SCOPUS and Web of Science (from inception to November 2014) databases. Meta-analyses were performed using inverse variance with random effects models. The GRADE system was used to rate the quality of the evidence. A P-value lower than 0.05 was considered significant. Results: A total of four RCTs were included in the meta-analyses (1,528 patients) with follow up ranging from 2 to 20 years. Three used old generation mechanical and biological prostheses, and one used contemporary prostheses. No significant difference in mortality was found between BP and MP patients (risk ratio (RR = 1.07; 95% CI 0.99-1.15). The risk of bleeding was significantly lower in BP patients than MP patients (RR = 0.64; 95% CI 0.52-0.78); however, reoperations were significantly more frequent in BP patients (RR = 3.60; 95% CI 2.44-5.32). There were no statistically significant differences between BP and MP patients with respect to systemic arterial embolisms and infective endocarditis (RR = 0.93; 95% CI 0.66-1.31, RR = 1.21; CI95% 0.78-1.88, respectively). Results in the trials with modern and old prostheses were similar. Conclusions: The mortality rate and the risk of thromboembolic events and endocarditis were similar between BP and MP patients. The risk of bleeding was approximately one third lower for BP patients than for MP patients, while the risk of reoperations was more than three times higher for BP patients.

RESUMO Objetivo: Avaliar a prevalência de incapacidades físicas, cognitivas e psiquiátricas, fatores associados e sua relação com qualidade de vida em pacientes sobreviventes de internação em unidades de terapia intensiva brasileiras. Métodos: Um estudo de coorte prospectivo multicêntrico está sendo conduzido em dez unidades de terapia intensiva adulto clínico-cirúrgicas representativas das cinco regiões geopolíticas do Brasil. Pacientes com idade ≥ 18 anos que receberam alta das unidades de terapia intensiva participantes e permaneceram internados na unidade de terapia intensiva por 72 horas ou mais, nos casos de internação clínica ou cirúrgica de urgência, e por 120 horas ou mais, nos casos de internação cirúrgica eletiva, serão incluídos de forma consecutiva. Estes pacientes serão seguidos por 1 ano, por meio de entrevistas telefônicas estruturadas 3, 6 e 12 meses pós-alta da unidade de terapia intensiva. Dependência funcional, disfunção cognitiva, sintomas de ansiedade e depressão, sintomas de estresse pós-traumático, qualidade de vida relacionada à saúde, re-hospitalizações e mortalidade em longo prazo serão avaliados como desfechos. Discussão: O presente estudo tem o potencial de contribuir para o conhecimento a respeito da prevalência e dos fatores associados à síndrome pós-cuidados intensivos na população de pacientes adultos sobreviventes de internação em unidades de terapia intensiva brasileiras. Ademais, a associação entre síndrome pós-cuidados intensivos e qualidade de vida relacionada à saúde poderá ser estabelecida.

BACKGROUND:In 2007, the Saline versus Albumin Fluid Evaluation-Translation of Research Into Practice Study (SAFE-TRIPS) reported that 0.9% sodium chloride (saline) and hydroxyethyl starch (HES) were the most commonly used resuscitation fluids in intensive care unit (ICU) patients. Evidence has emerged since 2007 that these fluids are associated with adverse patient-centred outcomes. Based on the published evidence since 2007, we sought to determine the current type of fluid resuscitation used in clinical practice and the predictors of fluid choice and determine whether these have changed between 2007 and 2014. METHODS:In 2014, an international, cross-sectional study was conducted (Fluid-TRIPS) to document current patterns of intravenous resuscitation fluid use and determine factors associated with fluid choice. We examined univariate and multivariate associations between patients and prescriber characteristics, geographical region and fluid type. Additionally, we report secular trends of resuscitation fluid use in a cohort of ICUs that participated in both the 2007 and 2014 studies. Regression analysis were conducted to determine changes in the administration of crystalloid or colloid between 2007 and 2014. FINDINGS:In 2014, a total of 426 ICUs in 27 countries participated. Over the 24 hour study day, 1456/6707 (21.7%) patients received resuscitation fluid during 2716 resuscitation episodes. Crystalloids were administered to 1227/1456 (84.3%) patients during 2208/2716 (81.3%) episodes and colloids to 394/1456 (27.1%) patients during 581/2716 (21.4%) episodes. In multivariate analyses, practice significantly varied between geographical regions. Additionally, patients with a traumatic brain injury were less likely to receive colloid when compared to patients with no trauma (adjusted OR 0.24; 95% CI 0.1 to 0.62; p = 0.003). Patients in the ICU for one or more days where more likely to receive colloid compared to patients in the ICU on their admission date (adjusted OR 1.75; 95% CI 1.27 to 2.41; p =

Fundamento: Os modelos prognósticos disponíveis para Síndrome Coronariana Aguda (SCA) podem ter limitações de performance, por terem sido elaborados há vários anos, ou problemas de aplicabilidade. Objetivos: Elaborar escores para predição de eventos desfavoráveis em 30 dias e 6 meses, em pacientes com SCA, com ou sem Supradesnivelamento de ST (SST), atendida em hospital privado terciário. Métodos: Coorte prospectiva de pacientes consecutivos com SCA admitidos entre agosto/2009 a junho/2012. O desfecho primário composto foi a ocorrência de óbito, infarto ou reinfarto, Acidente Vascular Cerebral (AVC), parada cardiorrespiratória e sangramento maior. As variáveis preditoras foram selecionadas de dados clínicos, laboratoriais, eletrocardiográficos e da terapêutica. O modelo final foi obtido por meio de regressão logística e submetido a validação interna, utilizando-se bootstraping. Resultados: Incluímos 760 pacientes, 132 com SCA com SST e 628 sem SST. A idade média foi 63,2 ± 11,7 anos, sendo 583 homens (76,7%). O modelo final para eventos em 30 dias contém cinco preditores: idade ≥ 70 anos, antecedente de neoplasia, Fração de Ejeção do Ventrículo Esquerdo (FEVE) < 40%, troponinaI > 12,4 ng/mL e trombólise. Na validação interna, o modelo mostrou ter boa performance com área sob a curva de 0,71.Os preditores do modelo para 6 meses são: antecedente de neoplasia, FEVE < 40%, trombólise, troponina I > 14,3 ng/mL, creatinina > 1,2 mg/dL, antecedente de doença pulmonar obstrutiva crônica e hemoglobina < 13,5 g/dL. Na validação interna, o modelo apresentou boa performance com área sob a curva de 0,69. Conclusões: Desenvolvemos escores de fácil utilização e boa performance para predição de eventos adversos em 30 dias e 6 meses em pacientes com SCA.

O suporte ventilatório artificial invasivo e não invasivo ao paciente crítico tem evoluído e inúmeras evidências têm surgido, podendo ter impacto na melhora da sobrevida e da qualidade do atendimento oferecido nas unidades de terapia intensiva no Brasil. Isto posto, a Associação de Medicina Intensiva Brasileira (AMIB) e a Sociedade Brasileira de Pneumologia e Tisiologia (SBPT) - representadas pelo seus Comitê de Ventilação Mecânica e Comissão de Terapia Intensiva, respectivamente, decidiram revisar a literatura e preparar recomendações sobre ventilação mecânica objetivando oferecer aos associados um documento orientador das melhores práticas da ventilação mecânica na beira do leito, baseado nas evidencias existentes, sobre os 29 subtemas selecionados como mais relevantes no assunto. O projeto envolveu etapas visando distribuir os subtemas relevantes ao assunto entre experts indicados por ambas as sociedades que tivessem publicações recentes no assunto e/ou atividades relevantes em ensino e pesquisa no Brasil na área de ventilação mecânica. Esses profissionais, divididos por subtemas em duplas, responsabilizaram-se por fazer revisão extensa da literatura mundial sobre cada subtema. Reuniram-se todos no Forum de Ventilação Mecânica na sede da AMIB em São Paulo, em 03 e 04 de agosto de 2013 para finalização conjunta do texto de cada subtema e apresentação, apreciação, discussão e aprovação em plenária pelos 58 participantes, permitindo a elaboração de um documento final.

Objective: To evaluate nurses’ perception regarding three differentblood glucose control protocols for critically ill patients. Methods:As part of a randomized trial comparing three blood glucose controlprotocols in critically ill patients (Computer-Assisted Insulin Protocol, Leuven Protocol, and conventional treatment), all nurses participating in the study were asked to fill in a questionnaire to assess their perceptions of efficacy, complexity, feasibility, and safety (as to the occurrence of hypoglycemic episodes), an to indicate which protocol they would like to see adopted as the standard one in the Intensive Care Unit they worked. Results: Sixty nurses answered the questionnaires. Computer-Assisted Insulin Protocol was considered the most efficient protocol to maintain blood glucose levels within the target range by 58% of the nurses, compared to 22% for Leuven Protocol (p

ABSTRACT Objective: To compare efficacy and safety of vancomycin versus teicoplanin in patients with proven or suspected infection. Methods: Data Sources: Cochrane Renal Group's Specialized Register, CENTRAL, MEDLINE, EMBASE, nephrology textbooks and review articles. Inclusion criteria: Randomized controlled trials in any language comparing teicoplanin to vancomycin for patients with proven or suspected infection. Data extraction: Two authors independently evaluated methodological quality and extracted data. Study investigators were contacted for unpublished information. A random effect model was used to estimate the pooled risk ratio (RR) with 95% confidence interval (CI). Results: A total of 24 studies (2,610 patients) were included. The drugs had similar rates of clinical cure (RR: 1.03; 95%CI: 0.98-1.08), microbiological cure (RR: 0.98; 95%CI: 0.93-1.03) and mortality (RR: 1.02; 95%CI: 0.79-1.30). Teicoplanin had lower rates of skin rash (RR: 0.57; 95%CI: 0.35-0.92), red man syndrome (RR: 0.21; 95%CI: 0.08-0.59) and total adverse events (RR: 0.73; 95%CI: 0.53-1.00). Teicoplanin reduced the risk of nephrotoxicity (RR: 0.66; 95%CI: 0.48-0.90). This effect was consistent for patients receiving aminoglycosides (RR: 0.51; 95%CI: 0.30-0.88) or having vancomycin doses corrected by serum levels (RR: 0.22; 95%CI: 0.10-0.52). There were no cases of acute kidney injury needing dialysis. Limitations: Studies lacked a standardized definition for nephrotoxicity. Conclusions: Teicoplanin and vancomycin are equally effective; however the incidence of nephrotoxicity and other adverse events was lower with teicoplanin. It may be reasonable to consider teicoplanin for patients at higher risk for acute kidney injury.

Ensaios clínicos aleatorizados são investigações científicas consideradas padrão-ouro para avaliar intervenções terapêuticas. Ensaios clínicos aleatorizados podem examinar e avaliar a segurança e eficácia de novas drogas ou procedimentos terapêuticos ou comparar os efeitos entre duas ou mais drogas ou qualquer outra intervenção. Nesse artigo apresentamos as características essenciais e fatores que podem introduzir viés nesses estudos. Em seguida, apresentamos critérios para avaliação crítica de artigos reportando os resultados de ensaios clínicos aleatorizados e mostramos como interpretar e aplicá-los à prática clínica.Randomized controlled trials are scientific investigations considered as the gold-standard to evaluate therapeutic interventions. Randomized controlled trials may examine the safety and efficacy of new drugs and therapeutic procedures or compare the effects of two or more drugs or any other intervention. In this article, we present the essential features of these studies, as well as, factors which may bias randomized controlled trials. We also present criteria to critically appraise articles reporting randomized controlled trials, explain how to interpret the results and how to apply them to clinical practice.

Pulmonary embolism is a potentially lethal disorder, consequent tothrombi formed in the deep venous system that, once detached,cross the right chambers of the heart, thus obstructing the pulmonaryartery or one of its branches. Mortality rate associated to untreatedembolism is approximately 30%. A quick diagnosis is crucial, sincetreatment reduces mortality and morbidity, and improves the qualityof life for reducing the likelihood of thromboembolic pulmonaryhypertension and post-thrombotic syndrome. The objective of thisarticle is to present a literature review on this condition, divided intotwo parts. On the first part we approach the practical aspects of itsepidemiology, pathophysiology, identification of risk factors, clinical,laboratorial and imaging diagnostic methods. On the second, themain aspects of its medical and surgical treatments are addressed.

Current guidelines and consensus recommend arterial and venous samples as equally acceptable for blood glucose assessment in point-of-care devices, but there is limited evidence to support this recommendation. We evaluated the accuracy of two devices for bedside point-of-care blood glucose measurements using arterial, fingerstick and catheter venous blood samples in ICU patients, and assessed which factors could impair their accuracy.145 patients from a 41-bed adult mixed-ICU, in a tertiary care hospital were prospectively enrolled. Fingerstick, central venous (catheter) and arterial blood (indwelling catheter) samples were simultaneously collected, once per patient. Arterial measurements obtained with Precision PCx, and arterial, fingerstick and venous measurements obtained with Accu-chek Advantage II were compared to arterial central lab measurements. Agreement between point-of-care and laboratory measurements were evaluated with Bland-Altman, and multiple linear regression models were used to investigate interference of associated factors.Mean difference between Accu-chek arterial samples versus central lab was 10.7 mg/dL (95% LA -21.3 to 42.7 mg/dL), and between Precision PCx versus central lab was 18.6 mg/dL (95% LA -12.6 to 49.5 mg/dL). Accu-chek fingerstick versus central lab arterial samples presented a similar bias (10.0 mg/dL) but a wider 95% LA (-31.8 to 51.8 mg/dL). Agreement between venous samples with arterial central lab was the poorest (mean bias 15.1 mg/dL; 95% LA -51.7 to 81.9). Hyperglycemia, low hematocrit, and acidosis were associated with larger differences between arterial and venous blood measurements with the two glucometers and central lab. Vasopressor administration was associated with increased error for fingerstick measurements.Sampling from central venous catheters should not be used for glycemic control in ICU patients. In addition, reliability of the two evaluated glucometers was insufficient. Error with Accu-chek Advantage II increases mostly with central venous samples. Hyperglycemia, lower hematocrit, acidosis, and vasopressor administration increase measurement error.

JUSTIFICATIVA E OBJETIVOS: Os princípios da Medicina baseada em evidências têm sido aplicados à Anestesiologia. A proposta dessa revisão é abordar os fundamentos para a prática da Medicina baseada em evidências e fornecer exemplos de como esses princípios podem ser incorporados à prática diária. Até o momento da conclusão desse artigo, não foi encontrado nenhum trabalho sobre Anestesiologia baseada em evidências na literatura médica brasileira, o que determinou a sua realização. CONTEÚDO: Este artigo consiste de revisão que aborda um novo paradigma da Medicina e como ele pode ser aplicado à Anestesiologia. CONCLUSÕES: A Anestesiologia baseada em evidências constitui a integração da melhor evidência científica disponível à experiência clínica do anestesiologista e às expectativas do paciente, visando à melhoria do cuidado com ele.JUSTIFICATIVA Y OBJETIVOS: Los principios de la Medicina fundamentados en evidencias han sido aplicados a la Anestesiología. La propuesta de esa revisión es abordar los fundamentos para la práctica de la Medicina fundamentados en evidencias y proporcionar ejemplos de como eses principios pueden ser incorporados a la práctica diaria. Hasta el momento de la conclusión de ese artículo, no fue encontrado ningún trabajo sobre Anestesiología fundamentados en evidencias en la literatura médica brasileña, lo que determinó su realización. CONTENIDO: Este artículo consiste en una revisión que aborda un nuevo paradigma de la Medicina y como él puede ser aplicado a la Anestesiología. CONCLUSIONES: La Anestesiología fundamentada en evidencias constituye la integración de la mejor evidencia científica disponible a la experiencia clínica del anestesiologista y a las expectativas del paciente, con la finalidad de la mejoría y cuidado con él.BACKGROUND AND OBJECTIVES: The principles of evidence-based medicine have been applied to Anesthesiology. The purpose of this article is to review the basis for the practice of evidence-based medicine and give some examples of how its principles may be incorporated to the clinical practice. We couldn't find any article about this issue in the Brazilian medical literature and decided to perform it. CONTENTS: This study is a review focusing on a new medical paradigm and how it can be applied to Anesthesiology. CONCLUSIONS: Evidence-Based Anesthesiology is the integration of best scientific evidence, anesthesiologists' clinical experience and patients' expectations, aiming at improving patients' care.