The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The Financing of Industry, 1970-89: An International Comparison.

The main aims of this paper are, first, to construct a consistent comparative set of data on the sources of finance for investment over the period 1970--89 for Germany, Japan, the United Kingdom and the United States and second, to challenge some conventional views of the international differences in financing patterns. The paper documents the substantial problems of international comparisons, and argues that net sources and using data based on National Income Accounts provide the most appropriate and consistent information. We conclude that there is no 'market-based' Anglo-US pattern of financing of industry. Germany, the United Kingdom and the United States are internally financed with small or negative contributions from market sources. Japan has been more externally financed with both banks and markets contributing larger shares than in the former group. Over the 1980s, the period of financial liberalization, all countries, except Japan, have become more internally and less market financed

The Financing of Industry, 1970-89: An International Comparison

The main aims of this paper are, first, to construct a consistent comparative set of data on the sources of finance for investment over the period 1970--89 for Germany, Japan, the United Kingdom and the United States and second, to challenge some conventional views of the international differences in financing patterns. The paper documents the substantial problems of international comparisons, and argues that net sources and using data based on National Income Accounts provide the most appropriate and consistent information. We conclude that there is no `market-based' Anglo-US pattern of financing of industry. Germany, the United Kingdom and the United States are internally financed with small or negative contributions from market sources. Japan has been more externally financed with both banks and markets contributing larger shares than in the former group. Over the 1980s, the period of financial liberalization, all countries, except Japan, have become more internally and less market financed.Corporate Finance; International Comparisons; Investment

Flow Energy Piezoelectric Bimorph Nozzle Harvester

There is a need for a long-life power generation scheme that could be used downhole in an oil well to produce 1 Watt average power. There are a variety of existing or proposed energy harvesting schemes that could be used in this environment but each of these has its own limitations. The vibrating piezoelectric structure is in principle capable of operating for very long lifetimes (decades) thereby possibly overcoming a principle limitation of existing technology based on rotating turbo-machinery. In order to determine the feasibility of using piezoelectrics to produce suitable flow energy harvesting, we surveyed experimentally a variety of nozzle configurations that could be used to excite a vibrating piezoelectric structure in such a way as to enable conversion of flow energy into useful amounts of electrical power. These included reed structures, spring mass-structures, drag and lift bluff bodies and a variety of nozzles with varying flow profiles. Although not an exhaustive survey we identified a spline nozzle/piezoelectric bimorph system that experimentally produced up to 3.4 mW per bimorph. This paper will discuss these results and present our initial analyses of the device using dimensional analysis and constitutive electromechanical modeling. The analysis suggests that an order-of-magnitude improvement in power generation from the current design is possible

An assessment of interactions between global health initiatives and country health systems

Since 2000, the emergence of several large disease-specific global health initiatives (GHIs) has changed the way in which international donors provide assistance for public health. Some critics have claimed that these initiatives burden health systems that are already fragile in countries with few resources, whereas others have asserted that weak health systems prevent progress in meeting disease-specific targets. So far, most of the evidence for this debate has been provided by speculation and anecdotes. We use a review and analysis of existing data, and 15 new studies that were submitted to WHO for the purpose of writing this Report to describe the complex nature of the interplay between country health systems and GHIs. We suggest that this Report provides the most detailed compilation of published and emerging evidence so far, and provides a basis for identification of the ways in which GHIs and health systems can interact to mutually reinforce their effects. On the basis of the findings, we make some general recommendations and identify a series of action points for international partners, governments, and other stakeholders that will help ensure that investments in GHIs and country health systems can fulfil their potential to produce comprehensive and lasting results in disease-specific work, and advance the general public health agenda. The target date for achievement of the health-related Millennium Development Goals is drawing close, and the economic downturn threatens to undermine the improvements in health outcomes that have been achieved in the past few years. If adjustments to the interactions between GHIs and country health systems will improve efficiency, equity value for money, and outcomes in global public health, then these opportunities should not be missed

Effect of lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal vs standard care ventilation on 90-day mortality in patients with acute hypoxemic respiratory failure

Importance In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference