Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (+/- SD) of 5.3 +/- 2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P = 0.02). The number of serious adverse events did not differ significantly between the treatment groups (P = 0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation

Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences

Non peer reviewe

The seeds of divergence: the economy of French North America, 1688 to 1760

Generally, Canada has been ignored in the literature on the colonial origins of divergence with most of the attention going to the United States. Late nineteenth century estimates of income per capita show that Canada was relatively poorer than the United States and that within Canada, the French and Catholic population of Quebec was considerably poorer. Was this gap long standing? Some evidence has been advanced for earlier periods, but it is quite limited and not well-suited for comparison with other societies. This thesis aims to contribute both to Canadian economic history and to comparative work on inequality across nations during the early modern period. With the use of novel prices and wages from Quebec—which was then the largest settlement in Canada and under French rule—a price index, a series of real wages and a measurement of Gross Domestic Product (GDP) are constructed. They are used to shed light both on the course of economic development until the French were defeated by the British in 1760 and on standards of living in that colony relative to the mother country, France, as well as the American colonies. The work is divided into three components. The first component relates to the construction of a price index. The absence of such an index has been a thorn in the side of Canadian historians as it has limited the ability of historians to obtain real values of wages, output and living standards. This index shows that prices did not follow any trend and remained at a stable level. However, there were episodes of wide swings—mostly due to wars and the monetary experiment of playing card money. The creation of this index lays the foundation of the next component. The second component constructs a standardized real wage series in the form of welfare ratios (a consumption basket divided by nominal wage rate multiplied by length of work year) to compare Canada with France, England and Colonial America. Two measures are derived. The first relies on a “bare bones” definition of consumption with a large share of land-intensive goods. This measure indicates that Canada was poorer than England and Colonial America and not appreciably richer than France. However, this measure overestimates the relative position of Canada to the Old World because of the strong presence of land-intensive goods. A second measure is created using a “respectable” definition of consumption in which the basket includes a larger share of manufactured goods and capital-intensive goods. This second basket better reflects differences in living standards since the abundance of land in Canada (and Colonial America) made it easy to achieve bare subsistence, but the scarcity of capital and skilled labor made the consumption of luxuries and manufactured goods (clothing, lighting, imported goods) highly expensive. With this measure, the advantage of New France over France evaporates and turns slightly negative. In comparison with Britain and Colonial America, the gap widens appreciably. This element is the most important for future research. By showing a reversal because of a shift to a different type of basket, it shows that Old World and New World comparisons are very sensitive to how we measure the cost of living. Furthermore, there are no sustained improvements in living standards over the period regardless of the measure used. Gaps in living standards observed later in the nineteenth century existed as far back as the seventeenth century. In a wider American perspective that includes the Spanish colonies, Canada fares better. The third component computes a new series for Gross Domestic Product (GDP). This is to avoid problems associated with using real wages in the form of welfare ratios which assume a constant labor supply. This assumption is hard to defend in the case of Colonial Canada as there were many signs of increasing industriousness during the eighteenth and nineteenth centuries. The GDP series suggest no long-run trend in living standards (from 1688 to circa 1765). The long peace era of 1713 to 1740 was marked by modest economic growth which offset a steady decline that had started in 1688, but by 1760 (as a result of constant warfare) living standards had sunk below their 1688 levels. These developments are accompanied by observations that suggest that other indicators of living standard declined. The flat-lining of incomes is accompanied by substantial increases in the amount of time worked, rising mortality and rising infant mortality. In addition, comparisons of incomes with the American colonies confirm the results obtained with wages— Canada was considerably poorer. At the end, a long conclusion is provides an exploratory discussion of why Canada would have diverged early on. In structural terms, it is argued that the French colony was plagued by the problem of a small population which prohibited the existence of scale effects. In combination with the fact that it was dispersed throughout the territory, the small population of New France limited the scope for specialization and economies of scale. However, this problem was in part created, and in part aggravated, by institutional factors like seigneurial tenure. The colonial origins of French America’s divergence from the rest of North America are thus partly institutional

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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

Couches minces en Fe-N élaborées par implantation ionique : propriétés structurales et magnétiques

The alpha'-Fe8N1-x and alpha''-Fe16N2 phases have a high potential of application, because of their uniaxial magnetocrystalline anisotropy and their large saturation magnetization. However, the values announced for these magnetic properties remain a subject of discussion. The research conducted during this PhD thesis was initiated in order to clarify this situation. Sample making consisted mainly of nitrogen ion implantation into alpha-Fe thin films, epitaxially grown on ZnSe/GaAs (001). Among others, the effects of target temperature and fluence on the crystal structure of the samples were analyzed by X-ray diffractometry. The presence of a perpendicular magnetic anisotropy was demonstrated in the thin films containing the alpha'-Fe8N1-x and alpha''-Fe16N2 phases. The anisotropy constant was evaluated by vibrating sample magnetometry and ferromagnetic resonance. In this research, weak stripe domains were observed by magnetic force microscopy in some Fe-N thin films. These are particularly straight and edge dislocations are found within their periodic structure. Studies were then carried out to precisely control the reorientation of the stripe domains and the displacement of the magnetic dislocations, using a magnetic field.Les phases alpha'-Fe8N1-x et alpha''-Fe16N2 ont un fort potentiel d’application, en raison de leur anisotropie magnétocristalline uniaxiale et de leur grande aimantation à saturation. Cependant, les valeurs annoncées pour ces propriétés magnétiques restent sujettes à discussion. Les recherches menées au cours de cette thèse de doctorat ont été initiées dans le but de clarifier cette situation. L’élaboration des échantillons a principalement consisté en l’implantation ionique d’azote dans des couches minces de fer alpha épitaxiées sur ZnSe/GaAs (001). Entre autres, les effets de la température de la cible et de la fluence sur la structure cristalline des échantillons ont été analysés par diffractométrie des rayons X. La présence d’une anisotropie magnétique perpendiculaire a été mise en évidence dans les couches minces contenant les phases alpha'-Fe8N1-x ou alpha''-Fe16N2. La constante d’anisotropie a été évaluée par magnétométrie à échantillon vibrant et résonance ferromagnétique. À l’occasion de ces recherches, des domaines en rubans faibles ont été observés par microscopie à force magnétique dans certaines couches minces en Fe-N. Ceux-ci sont particulièrement rectilignes et des dislocations coin se trouvent au sein de leur structure périodique. Des études ont alors été réalisées dans le but de contrôler avec précision la réorientation des domaines en rubans et le déplacement des dislocations magnétiques, à l’aide d’un champ magnétique

Fe-N thin films made by ion implantation : structural and magnetic properties

Les phases alpha'-Fe8N1-x et alpha''-Fe16N2 ont un fort potentiel d’application, en raison de leur anisotropie magnétocristalline uniaxiale et de leur grande aimantation à saturation. Cependant, les valeurs annoncées pour ces propriétés magnétiques restent sujettes à discussion. Les recherches menées au cours de cette thèse de doctorat ont été initiées dans le but de clarifier cette situation. L’élaboration des échantillons a principalement consisté en l’implantation ionique d’azote dans des couches minces de fer alpha épitaxiées sur ZnSe/GaAs (001). Entre autres, les effets de la température de la cible et de la fluence sur la structure cristalline des échantillons ont été analysés par diffractométrie des rayons X. La présence d’une anisotropie magnétique perpendiculaire a été mise en évidence dans les couches minces contenant les phases alpha'-Fe8N1-x ou alpha''-Fe16N2. La constante d’anisotropie a été évaluée par magnétométrie à échantillon vibrant et résonance ferromagnétique. À l’occasion de ces recherches, des domaines en rubans faibles ont été observés par microscopie à force magnétique dans certaines couches minces en Fe-N. Ceux-ci sont particulièrement rectilignes et des dislocations coin se trouvent au sein de leur structure périodique. Des études ont alors été réalisées dans le but de contrôler avec précision la réorientation des domaines en rubans et le déplacement des dislocations magnétiques, à l’aide d’un champ magnétique.The alpha'-Fe8N1-x and alpha''-Fe16N2 phases have a high potential of application, because of their uniaxial magnetocrystalline anisotropy and their large saturation magnetization. However, the values announced for these magnetic properties remain a subject of discussion. The research conducted during this PhD thesis was initiated in order to clarify this situation. Sample making consisted mainly of nitrogen ion implantation into alpha-Fe thin films, epitaxially grown on ZnSe/GaAs (001). Among others, the effects of target temperature and fluence on the crystal structure of the samples were analyzed by X-ray diffractometry. The presence of a perpendicular magnetic anisotropy was demonstrated in the thin films containing the alpha'-Fe8N1-x and alpha''-Fe16N2 phases. The anisotropy constant was evaluated by vibrating sample magnetometry and ferromagnetic resonance. In this research, weak stripe domains were observed by magnetic force microscopy in some Fe-N thin films. These are particularly straight and edge dislocations are found within their periodic structure. Studies were then carried out to precisely control the reorientation of the stripe domains and the displacement of the magnetic dislocations, using a magnetic field

Casino de Monte-Carlo, 1878

Photographie: Hartill Art Associates. AFr-0721; Date du début des travaux de réalisation : 1878