O EPS visa detectar as alterações através da anamnese (ex: dados de identificação: relacionados a idade - risco de quedas e a polifarmácia - e relacionados ao gênero – triagem de neoplasia de colo de útero em mulheres e de próstata em homens; revisão de sistemas para avaliação da carteira vacinal e do vício de tabagismo); do exame físico, pela avaliação do risco cardiovascular através da mensuração da pressão arterial; e da realização de exames complementares visando a triagem de neoplasias (mama através realização de mamografia ou colorretal através da colonoscopia), triagem do risco cardiovascular através da dosagem do colesterol e da triagem de diabete mélito através da dosagem da hemoglobina glicada. Recomendações validadas devem ser aplicadas nas populações visando a triagem e, se possível, tratamento de doenças diagnosticadas precocemente. O objetivo desta revisão é a de apresentar de forma sucinta e pragmática as recomendações atuais de triagem de doenças prevalentes. As recomendações sobre imunização (vacinação) não serão abordadas neste texto.

Introduction: A C5a-specific mAb, vilobelimab (VILO), in a Phase 3 randomized, double-blind, placebo (P)-controlled study showed significant reduction in 28-d all-cause mortality in critically ill COVID-19 patients (pt) (Vlaar APJ et al. Lancel Respir Med 2022;10(12):1137-46). Aims and Objectives: To compare mortality worldwide and by region in severe ARDS COVID-19 pt treated with VILO vs P. Methods: COVID-19 pt (N=368; VILO n=177, P n=191) were intubated within 48 hrs before 6, 800mg infusions of VILO or P on top of standard-of-care. Prespecified and posthoc analyses were performed worldwide and by region [Western Europe (WE), South America (SA), Russia/South Africa (RSA)] for mortality in severe ARDS pt with PaO2/FiO2<100 mmHg. Results: Median age (VILO 58 vs P 57 yrs), sex (~70% male) and severe ARDS pt were similar (VILO n=43, 24.3%; P n=55, 28.8%). VILO significantly reduced relative all-cause 28-d mortality worldwide in severe ARDS pt by 32.8% (HR 0.55; 95% CI:0.30-0.98;P=0.044). By region, VILO showed a nonsignificant 28-d mortality reduction trend (HR 0.37; 95% CI:0.11-1.22;P=0.058) in WE but SA (HR 1.03; 95% CI:0.040-2.70;P=0.944) and RSA (HR 0.37; 95% CI:0.11-1.22;P=0.102) showed lesser effects likely due to a younger P group median age in SA (VILO 50.0 vs P 45.5 yrs) and small numbers of severe ARDS pt in RSA. Treatment-emergent AEs, serious AEs and infection incidence per 100 pt days were equal per group with no meningococcal infections. Conclusion: Vilobelimab demontrated a significant worldwide reduction in all-cause mortality in severe ARDS COVID-19 pt with detected differences in three prespecified regions which may have been impacted by low pt numbers and an uneven age distribution in SA.

Abstract Background SARS-CoV-2 induces endothelial damage and activates the complement system. In severe COVID-19 patients, complement split factor C5a is highly elevated leading to inflammation that contributes to multiorgan failure. The anti-C5a monoclonal antibody, Vilobelimab (Vilo), which preserves the membrane attack complex (MAC), was investigated in an adaptively designed, randomized double-blind, placebo (P)-controlled Phase 3 international multicenter study for survival in critically ill COVID-19 patients (pts). Methods COVID-19 pneumonia pts (N=368; Vilo n=177, P n=191), mechanically ventilated within 48 hrs before treatment, received up to 6, 800 mg infusions of Vilo or P on top of standard of care. The primary and main secondary endpoints were 28-day (d) and 60-d all-cause mortality. Results Pts enrolled in the study were on corticosteroids (97%) and anti-coagulants (98%) as standard of care. A smaller proportion (20%) were either continuing or had taken immunomodulators such as tocilizumab and baricitinib prior to receiving Vilo. The 28-d all-cause mortality was 31.7% with Vilo vs 41.6% with P (Kaplan-Meier estimates; Cox regression site-stratified, HR 0.73; 95% CI:0.50-1.06; P=0.094), representing a 23.8% relative mortality reduction. In predefined primary outcome analysis without site stratification, however, Vilo significantly reduced mortality at 28 (HR 0.67; 95% CI:0.48-0.96; P=0.027) and 60 days (HR 0.67; 95% CI:0.48-0.92; P=0.016). Vilo also significantly reduced 28-d mortality in more severe pts with baseline WHO ordinal scale score of 7 (n=237, HR 0.62; 95% CI:0.40-0.95; P=0.028), severe ARDS/PaO2/FiO2 ≤ 100 mmHg (n=98, HR 0.55; 95% CI:0.30-0.98; P=0.044) and eGFR < 60 mL/min/1.73m2 (n=108, HR 0.55; 95% CI:0.31-0.96; P=0.036). Treatment-emergent AEs were 90.9% Vilo vs 91.0% P. Infections were comparable: Vilo 62.9%, P 59.3%. Infection incidence per 100 Pt days were equal. No meningococcal infections were reported. Serious AEs were 58.9% Vilo, 63.5% P. Conclusion Vilo significantly reduced mortality at 28 and 60 days in critically ill COVID-19 pts with no increase in infections suggesting the importance of targeting C5a while preserving MAC. Vilo targets inflammation which may represent an approach to treat sepsis and ARDS caused by other respiratory viruses. Disclosures Alexander Vlaar, MD, PhD, InflaRx GmbH: Advisor/Consultant Maria Habel, PhD, InflaRx GmbH: Stocks/Bonds Claus Thielert, PhD, InflaRx GmbH: Stocks/Bonds James Dickinson, MSc, InflaRx GmbH: Stocks/Bonds simon Rückinger, PhD, InflaRx GmbH: Advisor/Consultant Robert Zerbib, MSc, InflaRx GmbH: Stocks/Bonds Dorothee Neukirchen, PhD, InflaRx GmbH: Stocks/Bonds Korinna Pilz, MD, MSc, InflaRx GmbH: Ownership Interest|InflaRx GmbH: Stocks/Bonds Renfeng Guo, MD, InflaRx GmbH: Board Member|InflaRx GmbH: CSO|InflaRx GmbH: Ownership Interest|InflaRx GmbH: Stocks/Bonds Diederik van de Beek, MD, PhD, InflaRx GmbH: Advisor/Consultant Niels Riedemann, MD, PhD, InflaRx GmbH: Board Member|InflaRx GmbH: CEO|InflaRx GmbH: Ownership Interest|InflaRx GmbH: Stocks/Bonds.

Background Vilobelimab, an anti-C5a monoclonal antibody, was shown to be safe in a phase 2 trial of invasively mechanically ventilated patients with COVID-19. Here, we aimed to determine whether vilobelimab in addition to standard of care improves survival outcomes in this patient population. Methods This randomised, double-blind, placebo-controlled, multicentre phase 3 trial was performed at 46 hospitals in the Netherlands, Germany, France, Belgium, Russia, Brazil, Peru, Mexico, and South Africa. Participants aged 18 years or older who were receiving invasive mechanical ventilation, but not more than 48 h after intubation at time of first infusion, had a PaO 2/FiO 2 ratio of 60-200 mm Hg, and a confirmed SARS-CoV-2 infection with any variant in the past 14 days were eligible for this study. Eligible patients were randomly assigned (1:1) to receive standard of care and vilobelimab at a dose of 800 mg intravenously for a maximum of six doses (days 1, 2, 4, 8, 15, and 22) or standard of care and a matching placebo using permuted block randomisation. Treatment was not continued after hospital discharge. Participants, caregivers, and assessors were masked to group assignment. The primary outcome was defined as all-cause mortality at 28 days in the full analysis set (defined as all randomly assigned participants regardless of whether a patient started treatment, excluding patients randomly assigned in error) and measured using KaplanMeier analysis. Safety analyses included all patients who had received at least one infusion of either vilobelimab or placebo. This study is registered with ClinicalTrials.gov, NCT04333420. Findings From Oct 1, 2020, to Oct 4, 2021, we included 368 patients in the ITT analysis ( full analysis set; 177 in the vilobelimab group and 191 in the placebo group). One patient in the vilobelimab group was excluded from the primary analysis due to random assignment in error without treatment. At least one dose of study treatment was given to 364 (99%) patients (safety analysis set). 54 patients (31%) of 177 in the vilobelimab group and 77 patients (40%) of 191 in the placebo group died in the first 28 days. The all-cause mortality rate at 28 days was 32% (95% CI 25-39) in the vilobelimab group and 42% (35-49) in the placebo group (hazard ratio 0 center dot 73, 95% CI 0 center dot 50-1 center dot 06; p=0 center dot 094). In the predefined analysis without site-stratification, vilobelimab significantly reduced all-cause mortality at 28 days (HR 0 center dot 67, 95% CI 0 center dot 48-0 center dot 96; p=0 center dot 027). The most common TEAEs were acute kidney injury (35 [20%] of 175 in the vilobelimab group vs 40 [21%] of 189 in the placebo), pneumonia (38 [22%] vs 26 [14%]), and septic shock (24 [14%] vs 31 [16%]). Serious treatment-emergent adverse events were reported in 103 (59%) of 175 patients in the vilobelimab group versus 120 (63%) of 189 in the placebo group. Interpretation In addition to standard of care, vilobelimab improves survival of invasive mechanically ventilated patients with COVID-19 and leads to a significant decrease in mortality. Vilobelimab could be considered as an additional therapy for patients in this setting and further research is needed on the role of vilobelimab and C5a in other acute respiratory distress syndrome-causing viral infections.

BACKGROUND: Survivors of critical care may demonstrate mental health disorders in the months after discharge. RESEARCH QUESTION: What are risk factors for mental health disorders after ICU discharge and is there an association between the burden of mental illness and health-related quality of life (HRQoL)? STUDY DESIGN AND METHODS: Multicenter prospective cohort study that included 579 adult ICU survivors with an ICU stay of > 72 h in 10 ICUs. RESULTS: The outcomes were anxiety and depression assessed by the Hospital Anxiety and Depression Scale, posttraumatic stress disorder (PTSD) assessed by the Impact Event Scale 6, and HRQoL assessed by the Short Form 12 version 2. The 6-month prevalences of any mental health disorder were 36.2% (the prevalences of anxiety, depression, and PTSD were 24.2%, 20.9%, and 15.4%, respectively). ICU survivors with mental health disorders showed worse HRQoL scores in both physical and mental dimensions than those without. The higher the number of psychiatric syndromes manifested, the worse the mental dimension of HRQoL. Age of < 65 years (P = .009), history of depression (P = .009), anxiety (P = .003) and depression (P = .02) symptoms at ICU discharge, physical dependence (P = .01), and decreased physical functional status (P = .04) at 6 months were associated with anxiety. History of depression (P = .001), depression symptoms at ICU discharge (P < .001), and decreased physical functional status at 6 months (P = .01) were associated with depression. Depression symptoms at ICU discharge (P = .01), physical dependence (P = .01), and decreased physical functional status (P = .02) at 6 months were associated with PTSD. INTERPRETATION: The network of potential risk factors for mental illness among patients discharged from an ICU is complex and involves multiple factors (age, premorbid mental health, acute emotional stress, and physical impairment after ICU stay). The negative impact of the burden of mental illness on HRQoL among critical care survivors is of concern.

OBJECTIVE:To establish the prevalence of physical, cognitive and psychiatric disabilities, associated factors and their relationship with the qualities of life of intensive care survivors in Brazil.METHODS:A prospective multicenter cohort study is currently being conducted at 10 adult medical-surgical intensive care units representative of the 5 Brazilian geopolitical regions. Patients aged ≥ 18 years who are discharged from the participating intensive care units and stay 72 hours or more in the intensive care unit for medical or emergency surgery admissions or 120 hours or more for elective surgery admissions are consecutively included. Patients are followed up for a period of one year by means of structured telephone interviews conducted at 3, 6 and 12 months after discharge from the intensive care unit. The outcomes are functional dependence, cognitive dysfunction, anxiety and depression symptoms, posttraumatic stress symptoms, health-related quality of life, rehospitalization and long-term mortality.DISCUSSION:The present study has the potential to contribute to current knowledge of the prevalence and factors associated with postintensive care syndrome among adult intensive care survivors in Brazil. In addition, an association might be established between postintensive care syndrome and health-related quality of life.

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.