Study of the mechanisms involved in the regulation of O2 consumption kinetics during exercise.

Lors d’un exercice à une intensité au-dessous du seuil ventilatoire 1 (V1), la réponse fondamentale de la cinétique de la consommation de dioxygène (V̇ O2) s'élève de manière mono- exponentielle, atteignant un état stable après quelques minutes. Cependant, lors de l'exercice à une charge de travail constante au-dessus de V1, la cinétique de V̇ O2 est caractérisée par un début de l’état stable retardé et une deuxième augmentation de V̇ O2 superposée à la réponse initiale de V̇ O2.Cette augmentation lente de V̇ O2 est appelée la composante lente (V̇ O2sc). Il a été proposé que cet excès de V̇ O2, reflet de l'inefficacité musculaire, provienne principalement des muscles exercitant; cependant, à ce jour, les mécanismes putatifs à cette augmentation sont toujours mal compris. Plusieurs théories ont été proposées, parmi lesquels : a) la combinaison de processus liés à la fatigue nécessitant un recrutement supplémentaire de fibres pour compenser les fibres déjà fatiguées, et b) l'influence potentielle des différents profils métaboliques de différentes populations de types de fibres. Le but de cette thèse est de clarifier et de nourrir le débat sur les causes de V̇ O2sc, en particulier pour ces deux derniers paradigmes. Trois expérimentations ont été réalisées pour mesurer la concordance et les interférences de différentes cinétiques de fibres musculaires et la fatigue musculaire avec la V̇ O2sc. Les résultats de cette thèse sont les suivants : 1) Lors d’un exercice difficile, l'altération des propriétés neuromusculaires des extenseurs du genou (reflétant les processus de fatigue) n’a été significativement réduite qu’après 20-30 min d'exercice, alors que la V̇ O2sc avait fini de croitre. Ce résultat suggère qu'une relation temporelle entre la fatigue et la V̇ O2sc ne semble pas exister et, par conséquent, le développement de la fatigue n'est pas une condition essentielle pour le développement de la V̇ O2sc. 2) La fonction neuromusculaire évaluée à l’aide d’une stimulation double (Ddb, 100 Hz) pendant l'exercice d'extension du genou n'a pas été altérée dans le domaine difficile. En revanche, dans le domaine intense, la diminution significative de la force maximale et du taux maximal de développement de la force lors de la Ddb, reflétaient des processus de fatigue et étaient partiellement corrélées au développement de V̇ O2sc relatif. Par conséquent, les résultats suggéraient que la V̇ O2sc dans les domaines difficiles et intenses n'est pas le produit d'un mécanisme identique. 3) Afin de construire une nouvelle courbe combinant les principes de Henneman et de superposition, les trois courbes de transitions (repos-modérée, modérée-difficile et difficile-intense) ont été alignées dans le temps et sommées. Les résultats ont montré que globalement les paramètres de la cinétique de la courbe reconstruite n'étaient pas significativement différents d'une transition depuis le repos à un exercice d'intensité intense. Cela suggère que le recrutement supplémentaire de fibres n'était pas présent et que l'apparition de V̇ O2sc est au moins liée, sinon le résultat, des différentes propriétés métaboliques des fibres musculaires. Ces résultats évidence, lors de l'exercice chez l'homme, que les processus de fatigue représentés par des altérations des propriétés neuromusculaires ne sont pas une condition sine qua non pour le développement de la V̇ O2sc dans le domaine difficile, et que l'apparition du V̇ O2sc pourrait être le iétés métaboliques des fibres musculaires. -- Below the gas exchange threshold (GET), the fundamental response of O2 consumption (V̇ O2) kinetics rises monoexponentially, reaching a steady state after a few minutes. However, at a constant work rate exceeding the GET, the response is characterized by a delayed onset and a second rise in V̇ O2 superimposed on the initial V̇ O2 response. This slowly developing rise in V̇ O2 is termed the slow component (V̇ O2SC). This excess of V̇ O2, a reflection of muscle inefficiency, has been proposed to arise primarily from the exercising muscles; however, to date, the putative mechanisms are poorly understood. Several theories have been proposed, including the combination of fatigue-related processes requiring additional fiber recruitment to compensate for the already fatigued fibers and the potential influence of the different metabolic profiles of different fiber-type populations. The aim of this thesis is to clarify and nourish the debate on the causes of the V̇ O2SC, especially for these last two paradigms. Three different experiments were performed to measure the concordance and interferences of different kinetics of muscle fibers and muscle fatigue with the V̇ O2SC. The findings of this thesis are as follows: 1) During exercise at heavy intensity, the alteration in the neuromuscular properties of the knee extensors (reflecting fatigue processes) was significantly reduced after only 20-30 min of exercise, while the V̇ O2SC was stable. The results suggest that a temporal relationship between fatigue and the V̇ O2SC does not appear to exist; therefore, the development of fatigue is not an essential requirement to elicit the V̇ O2SC. 2) Neuromuscular function assessed through doublet stimulation (Ddb, 100Hz) during knee extension exercise was not altered in the heavy domain. In contrast, in the severe domain, the significant diminution in maximal force and maximal rate of force development during the Ddb, reflected fatigue processes and were partially correlated with the development of the relative V̇ O2sc. Therefore, the results suggest that the V̇ O2sc in the heavy and severe domains is not the product of an identical mechanism. 3) After constructing a new kinetics curve combining the Henneman and superposition principles, the three different intensity curves (moderate, heavy and severe) were time aligned and summed. The results showed that overall kinetics parameters from the reconstructed curve were not significantly different from one transition to severe-intensity exercise. This suggests that additional fiber recruitment was not present and that the appearance of the V̇ O2sc is at least related to, if not the result of, the different metabolic properties of muscle fibers. These results provide evidence in exercising humans that fatigue processes portrayed by alterations in neuromuscular properties are not a sine qua non for the development of the slow component in the heavy domain, and that, the appearance of the V̇ O2sc could be the result of the different metabolic properties of muscle fibers

AEEH «Consensus about detection and referral of hidden prevalent liver diseases»

Las enfermedades hepáticas constituyen una carga de enfermedad muy importante para nuestro sistema sanitario, tanto por su alta prevalencia como por su morbimortalidad asociada. La hepatitis C se ha considerado la principal causa de enfermedad hepática en los últimos 30 años, pero gracias al efectivo tratamiento antiviral directo y a las estrategias de cribado, actualmente su peso ha disminuido notablemente. La infección por virus de la hepatitis B sigue afectando a casi el 0,7% de la población...Peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Colombian consensus recommendations for diagnosis, management and treatment of the infection by SARS-COV-2/ COVID-19 in health care facilities - Recommendations from expert´s group based and informed on evidence

La Asociación Colombiana de Infectología (ACIN) y el Instituto de Evaluación de Nuevas Tecnologías de la Salud (IETS) conformó un grupo de trabajo para desarrollar recomendaciones informadas y basadas en evidencia, por consenso de expertos para la atención, diagnóstico y manejo de casos de Covid 19. Estas guías son dirigidas al personal de salud y buscar dar recomendaciones en los ámbitos de la atención en salud de los casos de Covid-19, en el contexto nacional de Colombia

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million 95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% 95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat