O cenário dos candidatos a vacina do COVID-19: existe alguma relação entre inovação e ambiente de negócios dos países?

The insurgency of the new coronavirus (SARS-COV-2) has attracted the attention of the public, authorities and academics. To date, no chemical treatment has proven efficient in clinical tests to combat the virus. The hope for the reopening of socioeconomic activities is found in the discovery of vaccines that can immunize people on a large scale. According to the World Health Organization, there are 29 vaccine candidates in the clinical evaluation phase and 138 candidates in the pre-clinical evaluation phase. In the race to discover a vaccine, there are initiatives from several laboratories and research centers. However, some countries stand out with a concentration of initiatives. This leads us to question whether this ability to promote research, development and seek innovation in the health field is not only associated with the size of economies, but also with the quality of the business environment. Thus, the aim of the present study is to explore the relationship between innovation and economic freedom, using econometric methodology (e.g. Panel Data Analysis) combined with non-parametric methodology (e.g., Data Envelopment Analysis). Our results allow us to infer how additional economic freedom can increase innovation for different levels of economic freedom within the countries. By doing so, we can explore why there is concentrated vaccine initiatives in few countries and a better understanding of the landscape for vaccine candidates of COVID-19.La insurgencia del nuevo coronavirus (SARS-COV-2) ha atraído la atención del público, las autoridades y los académicos. Hasta la fecha, ningún tratamiento químico ha demostrado ser eficiente en las pruebas clínicas para combatir el virus. La esperanza de la reanudación de las actividades socioeconómicas se encuentra en el descubrimiento de vacunas que pueden inmunizar a las personas a gran escala. Según la Organización Mundial de la Salud, hay 29 candidatos a vacunas en la fase de evaluación clínica y 138 candidatos en la fase de evaluación preclínica. En la carrera por descubrir una vacuna hay iniciativas de varios laboratorios y centros de investigación. Sin embargo, algunos países se destacan - hay una concentración de iniciativas. Esto nos lleva a cuestionarnos si esta capacidad para promover la investigación, el desarrollo y buscar la innovación en el campo de la salud no sólo está asociada con el tamaño de las economías, sino también con la calidad del entorno empresarial. Por lo tanto, el objetivo del presente estudio es explorar la relación entre innovación y libertad económica, utilizando la metodología econométrica (Análisis de Datos de Panel) combinada con la metodología no paramétrica (Análisis Envoltorio de Datos). Nuestros resultados nos permiten inferir cómo la libertad económica adicional puede aumentar la innovación para los diferentes niveles de libertad económica dentro de los países. Al hacerlo, podemos explorar por qué hay iniciativas de vacunas concentradas en pocos países y una mejor comprensión del panorama de los candidatos a vacunas de COVID-19.A insurgência do novo coronavírus (SARS-COV-2) tem atraído a atenção do público, autoridades e acadêmicos. Até o momento, nenhum tratamento químico se mostrou eficiente em testes clínicos para combater o vírus. A esperança de retomada das atividades socioeconômicas está na descoberta de vacinas que possam imunizar pessoas em larga escala. Segundo a Organização Mundial da Saúde, há 29 candidatos à vacina na fase de avaliação clínica e 138 candidatos na fase de avaliação pré-clínica. Na corrida para descobrir uma vacina há iniciativas de vários laboratórios e centros de pesquisa. No entanto, alguns países se destacam - há uma concentração de iniciativas. Isso nos leva a questionar se essa capacidade de promover pesquisa, desenvolvimento e buscar inovação no campo da saúde não está associada apenas ao tamanho das economias, mas também à qualidade do ambiente de negócios. Assim, o objetivo do presente estudo é explorar a relação entre inovação e liberdade econômica, utilizando metodologia econométrica (Análise de Dados em Painel) combinada com metodologia não paramétrica (Análise Envoltória de Dados). Nossos resultados nos permitem inferir como a liberdade econômica adicional pode aumentar a inovação para diferentes níveis de liberdade econômica dentro dos países. Ao fazê-lo, podemos explorar por que há iniciativas de vacinação concentradas em poucos países e uma melhor compreensão do cenário para os candidatos a vacinas do COVID-19.Revista do Serviço Público - RSP, v. 71, n. 4 p. 725-745Análise e Ciência de DadosGestão PúblicaPolítica Externa e Relações InternacionaisSaúdeISSN Eletrônico: 2357-8017ISSN Impresso: 0034-924

Correlation between isolated sonographic finding of umbilical cord cyst and fetal anomalies

OBJETIVO: Correlacionar o achado ultra-sonográfico isolado de cisto de cordão umbilical com anomalias fetais, como cromossomopatias e alterações estruturais. Segundo a literatura médica, as implicações clínicas do achado ultra-sonográfico de cisto de cordão nos segundo e terceiro trimestres de gestação estão bem estabelecidas, entretanto, quando no primeiro trimestre, o significado ainda permanece controverso. MATERIAIS E MÉTODOS: Foi realizado estudo retrospectivo de gestantes da população geral, consecutivas, com fetos únicos e vivos, que apresentavam apenas o achado de cisto de cordão umbilical, num período de dez anos (1996-2006). Em todos os casos foram realizados exames ultra-sonográficos para o rastreamento de anomalias fetais após o diagnóstico de cisto de cordão. Os recém-nascidos e o cordão umbilical foram examinados após o parto para se verificar a presença de anomalias. RESULTADOS: Foram estudados nove casos que apresentavam cisto de cordão umbilical como único achado, sem outros marcadores ultra-sonográficos de anomalias fetais. Detectaram-se dois casos no primeiro trimestre de gestação e sete nos segundo e terceiro trimestres. Dois casos foram submetidos a estudo citogenético fetal, por meio de amniocentese. Nenhum recém-nascido apresentou anomalias estruturais ou aneuploidia. CONCLUSÃO: O achado ultra-sonográfico isolado de cisto de cordão umbilical não significou aumento de risco para anomalias estruturais ou aneuploidias.OBJECTIVE: To correlate the isolated sonographic finding of umbilical cord cyst with fetal anomalies such as chromosomopathies and structural changes. According to the medical literature, the clinical implications of the sonographic finding of umbilical cord cyst in the second and third trimesters of pregnancy are well established; however, the meaning of this finding in the first trimester still remains controversial. MATERIALS AND METHODS: A retrospective study was developed with consecutive, pregnant women with single living fetuses presenting with umbilical cord cyst as an isolated finding, over a 10-year period (1996-2006). Ultrasound studies were performed in all cases for screening of fetal anomalies after the diagnosis of umbilical cord cyst. Neonates and umbilical cords were evaluated after delivery for the presence of abnormalities. RESULTS: Nine cases presenting umbilical cord cyst as a sole finding with no other sonographic marker for fetal abnormality were evaluated. Two cases were detected in the first pregnancy trimester and seven cases in the second and third trimesters. Fetal cytogenetic study was done by means of amniocentesis in two cases. No newborn presented with structural anomalies or aneuploidy. CONCLUSION: Isolated sonographic finding of umbilical cord cyst did not imply increased risk for fetal structural anomalies or aneuploidies

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Rewired glycosylation activity promotes scarless regeneration and functional recovery in spiny mice after complete spinal cord transection

Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies beta 3gnt7, a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth.Santa Casa da Misericordia de Lisboa MC-39-2019, Wings for Life WFL-PT-21/20, Portuguese Foundation for Science and Technology UID/BIM/04773/2013/CBMRinfo:eu-repo/semantics/publishedVersio

Immunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database

Background: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p &lt; 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p &lt; 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)

Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Background: Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS). Methods: An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared. Findings: 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved. Interpretation: More than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached