Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Çédille, revista de estudios franceses

Presentació

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Competências Propostas no Currículo de Medicina: Percepção do Egresso

RESUMO Introdução: As Diretrizes Curriculares Nacionais para cursos de Medicina trouxeram novos delineamentos de formação e desenvolvimento de habilidades e competências que instrumentalizam o médico para sua atuação. Objetivo: Identificar a percepção do egresso quanto à aquisição de competências e habilidades previstas no projeto pedagógico do curso de Medicina. Métodos: Estudo transversal com 229 egressos do curso de Medicina, entre 2005 e 2012, da Universidade Anhanguera-Uniderp de Campo Grande, Mato Grosso do Sul, por meio de questionário autoaplicável, no período de abril a julho de 2013, contendo 34 competências e habilidades, avaliadas por meio da escala do tipo Likert. Resultados: Quanto à aquisição de competências gerais, observaram-se respostas ″bom″ ou ″muito bom″ para a maioria dos itens pesquisados. Para a competência referente à comunicação, os maiores índices de respostas “muito bom” foram nos domínios “ser capaz de interagir e se articular com outros profissionais de saúde” (60%) e “ser capaz de manter a confidencialidade das informações” (68%). Em relação às competências específicas, a maior parte dos egressos referiu como “bom” ou ″muito bom″ a aquisição da maioria dos domínios. Observou-se ainda que os domínios “utilizar procedimentos diagnósticos e terapêuticos validados cientificamente″ e ″dominar os conhecimentos de fisiopatologia, do tratamento e reabilitação das doenças de maior prevalência″ tiveram os maiores índices de respostas ″bom″, 62% e 59%, respectivamente. No que se refere à aquisição de competências complementares, os domínios referentes às práticas gerais e específicas, tais como “estabelecer relação médico-paciente”, “realizar exame físico correlacionando com as referências anatômicas” e “realizar exame físico geral e segmentar”, atingiram maior percentual de respostas positivas (bom ou muito bom). Já os domínios referentes à “realização de exame especial neurológico”, “realização do exame especial ortopédico” e “imobilização de fraturas” apresentaram respostas ruins e regulares, que, somadas, corresponderam a 49%, 69% e 83%, respectivamente. Conclusões: O estudo serviu de base para mudanças no curso, fornecendo subsídios para melhoria da qualidade de ensino e respondendo às necessidades do acadêmico na graduação

Competencies Proposed in the Medical Curriculum: the Graduate’s Perception

<p></p><p>ABSTRACT Introduction: The Brazilian Education Guidelines for medical courses brought new designs for the education and development of abilities and competencies that qualify physicians for their practice. Objective: To identify the perception of graduates on the acquisition of abilities and competencies considered in the pedagogical project of a medical course. Methods: A cross-sectional study was developed with 229 graduates from a medical program carried out between 2005 and 2012, at UniversidadeAnhanguera-Uniderp in Campo Grande, in the state of Mato Grosso do Sul. The study involved the application of a self-administered questionnaire including 34 competencies and abilities, assessed through a Likert scale, from April to July 2013. Results: Regarding the acquisition of general competences, “good” or “very good” answers were found for most of the studied items. For the competency regarding communication, most of the “very good” answers were found in the domains “being capable of interacting with other health professionals” (60%) and “being capable of maintaining information confidentiality” (68%). As for specific competencies, the majority of the graduates referred to the acquisition of most domains as “good” or “very good”. The domains “using scientifically validated therapeutic and diagnostic procedures” and “mastering knowledge in physiopathology, treatment and rehabilitation of prevalent diseases” had the highest indices of “good” answers, 62% and 59%, respectively. As regards the acquisition of complementary competencies, the domains concerning general and specific practices, such as “establishing a physician-patient relationship”, “performing a physical exam correlating it to anatomical references” and “performing a general and segmentary physical exam” achieveda greater percentage of positive answers (good or very good). The domains regarding “performing a special neurological exam”, “performing a special orthopedic exam” and “immobilizing fractures” presented negative and regular answers, which when combined corresponded to 49%, 69% and 83%, respectively. Conclusions: The present study served as a basis for changes in the course, providing resources for improving the quality of education and meeting the graduates’ needs.</p><p></p

Presentation

El pasado mes de abril iniciamos una nueva etapa en Çédille, representada principalmente por su traslado a la plataforma Open Journal System (OJS) de la Universidad de La Laguna, así como por la renovación y reasignación de competencias del Consejo de Redacción. Durante este tiempo, hemos tenido que adaptarnos, experimentar y comprender, pacientemente, el funcionamiento de esta nueva herramienta que es OJS. Ello ha supuesto, en algunos casos, que se hayan producido determinadas dificultades de comunicación con nuestros lectores y evaluadores, o que se hayan ocasionado pequeños retrasos en la gestión de la revista. Como nuestros seguidores saben, muy recientemente hemos sufrido, además, un ataque informático que no solo impidió el acceso a la plataforma durante varios días (justo en el momento final de producción de este número), sino que obligó a trasladar nuestro sitio web a otro servidor y a implementar nuevas medidas de seguridad. Afortunadamente, gracias al buen hacer y profesionalidad de Juan Ascanio Amigó, asesor técnico de OJS para la Universidad de La Laguna, hemos logrado salir airosos de los problemas, complicaciones y secuelas que nos hemos ido encontrando en este tiempo. En este número que ahora ve la luz contamos con treinta y cuatro contri-buciones que superan, en total, las setecientas páginas. Así, Amelia Gamoneda Lanza y Francisco González Fernández se han encargado de coordinar una nueva entrega –la undécima– de la serie «Monografías», donde han reunido una ..

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p &lt; 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p &lt; 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p &lt; 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease

Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19 : a meta-analysis

IMPORTANCE Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. OBJECTIVE To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. DATA SOURCES Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts. STUDY SELECTION Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. DATA EXTRACTION AND SYNTHESIS In this prospectivemeta-analysis, risk of biaswas assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I-2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. MAIN OUTCOMES AND MEASURES The primary outcome measurewas all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days. RESULTS A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P =.003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P <.001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P =.52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16). CONCLUSIONS AND RELEVANCE In this prospectivemeta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality