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

Rethinking emotion as a natural kind: Correctives from Spinoza and hierarchical homology

It is commonly claimed that the folk category of emotion does not constitute a natural kind, due to the significant compositional differences between its members, especially basic and complex emotions. Arguably, however, this conclusion stems from the dualistic philosophical anthropology underlying the discussion, which presupposes a metaphysical “split” between mind and body. This is the case irrespective of whether a traditional or biological (homology-based) approach to natural kinds is adopted. Since the origins of this increasingly disputed anthropology can ultimately be traced to Descartes' substance dualism, its adverse effects can likewise be addressed using a contemporary theory of emotion developed from Spinoza, one of Descartes' earliest critics on this issue. Furthermore, a Spinozistic view of emotion accords with the recent shift to a hierarchical approach to homology, which recognises that the evolutionary lineage of complex biological units should be traced via relational qualities rather than physical characteristics. Both the Spinozistic approach to emotion and the hierarchical approach to homology show that the compositional variation in the folk category of emotion does not necessarily preclude it from constituting a natural kind

The cognitive/noncognitive debate in emotion theory: a corrective from Spinoza

An intractable problem that characterizes the contemporary philosophical discussion of emotion is whether emotions are fundamentally cognitive or noncognitive. In this article, I will establish that this problem arises from the influence of an underlying philosophical anthropology that entails a mind/body “split” ultimately inherited from Cartesianism, and further show that it can be fruitfully addressed by adopting a contemporary construal of the self and emotions derived from the philosophy of a key critic of Descartes dualism, Spinoza

Climate change effects on POPs’ environmental behaviour: a scientific perspective for future regulatory actions

Since the adoption of the United Nations Framework Convention on Climate Change, international efforts were aimed at limiting global change, and at managing and reducing its inevitable impacts. The growing concern on climate change related issues lead to create international agreements such as the Kyoto Protocol, and to establish the Intergovernmental Panel on Climate Change aimed at studying climate evolution and at defining common actions through the adoption of joint climate change mitigation and adaptation measures. From the time when international Task Forces, projects and programs were shared in order to deal with the reduction of environmental exposure to persistent organic pollutants (POPs), international organisations have also been committed to estimate how climate change may affect POPs’ environmental behaviour and distribution. In this review paper, we report the track of POPs’ regulation efforts driven towards decreasing POPs’ environmental concentrations through reducing or banning POP emissions in the environment. We also report scientific studies on climate change related effects on POPs’ environmental behaviour in order to feature how climate change is influencing POPs’ fate and transport. Our final aim is to identify how POPs–related regulations may take into account climate change in managing current or future POPs sources. We find in several case studies on this topic that climate change is considered to contribute to enhance POPs’ long–range transport and that remote areas are considered likely to be the most impacted by POPs’ pollution under a climate change perspective. Our findings also consider that continuous monitoring programs oriented towards the observation of secondary POP sources and the enhancement of inventories reporting primary and secondary POP emissions are useful in dealing with POPs’ exposure under climate change scenarios. We also suggest how communication between science and regulation should be driven towards considering climate change effects into chemicals’ legislation