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

Evaluating Claims of Early Human Occupation at Chiquihuite Cave, Mexico

Archaeologists working in Mexico recently claimed evidence for pre-Last Glacial Maximum human occupation in the Americas, based on lithic items excavated from Chiquihuite Cave, Zacatecas. Although they provide extensive array of ancillary studies of the cave's chronostratigraphic and paleoenvironmental record, the data they present do not support their central argument, that these lithic items are anthropogenic and represent a unique lithic industry produced by early human occupants. They give limited consideration to the most plausible alternative explanation: that the assemblage is a product of natural processes of disintegration, roof fall, and mass movement of the cave fill, and thus the lithic materials are best explained as geofacts. We assess the evidence by considering the alternative hypotheses (1) that the observed phenomena are artifacts or (2) that they result from natural processes. We conclude that hypothesis 2 is more strongly supported and that Chiquihuite Cave does not represent evidence for the earliest Americans.18 month embargo; published online: 23 October 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Current Understanding of the Earliest Human Occupations in the Americas: Evaluation of Becerra-Valdivia and Higham (2020)

Various chronologies of the earliest Native American occupations have been proposed with varying levels of empirical support and conceptual rigor, yet none is widely accepted. A recent survey of pre-Clovis dated sites (Becerra-Valdivia and Higham 2020) concludes a pre-Last Glacial Maximum (>26,500–19,000 cal yr BP) entry of humans in the Americas, in part based on recent work at Chiquihuite Cave, Mexico. We evaluate the evidence used to develop this inference. To provide clarity, we present three explicit dispersal models for the earliest human dispersals to the Americas: Strict Clovis-First (13,050 cal yr BP), Paleoindian (16,000 cal yr BP, encompassing pre-LGM, preferred by Becerra-Valdivia and Higham (2020)), and we summarize the current genetic and archaeological evidence bearing on each. We regard all purported Pre-Paleoindian sites as equivocal and the Strict Clovis-First model to be equally unsupported at present. We conclude that current data strongly support the Paleoindian Dispersal model, with Native American ancestors expanding into the Americas sometime after 16,000 cal yr BP (and perhaps after 14,800 cal yr BP), consistent with well-dated archaeological sites and with genetic data throughout the western hemisphere. Models of the Americas’ peopling that incorporate Chiquihuite or other claimed Pre-Paleoindian sites remain unsubstantiated.18 month embargo; published online: 23 October 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The ceramic ecology of florida: compositional baselines for pottery provenance studies

The success of pottery provenance studies is fundamentally dependent upon spatially patterned variation in the composition of exploited clay resources. Uniformity in clay composition within a region and recognizable differences between regions of interest are essential requirements for determining provenance, but these parameters are difficult to satisfy in study areas such as the coastal plain of the southeastern USA in which chemical and mineralogical variation tend toward continuous gradients. In an attempt to improve the reliability and validity of pottery provenance studies in the area, this research investigates compositional variation in raw clay samples from across Florida and southern Georgia through NAA (n=130) and petrographic analysis (n=99). The results indicate that fourteen distinct compositional regions can be differentiated, ranging from 50 km to 400 km in length. These regions dictate the direction and minimum distance a pottery vessel must have been transported in order to be recognized as nonlocal through compositional analysis. The validity of the proposed compositional regions is supported by previous case studies focused on assemblages from three of the regions. In each case, vessels were transported from other compositional regions more than 100 km away

The Transformation of Social Institutions in the North American Southeast

Corporate institutions, which transformed in the American Southeast over some 14,000 years, include social heterarchies and hierarchies that arose within the institutional contexts of descent groups, ritual sodalities, and social houses. The strategic and tactical actions of competitive and cooperative agents contributed to differing expressions of organizational changes through a variety of forms, including feasting, feuding/warfare, inalienable goods circulation, indebtedness, monumental constructions, mortuary events, processions/rogations, strategic marriages, and additional ritual and social practices. The nexus of social institutions that evolved along these pathways served as a catalyst for social changes, including the ways through which social institutions became transformed. Such social processes inform archaeologists of the agency, organization, and practice of people who not only invented and manipulated cosmologies, ideologies, institutions, and resources to achieve varying degrees of inequality, power, and wealth, but also those who resisted the efforts of aggrandizers. The author’s arguments focus on aristocratic social actions and actors, and the practices that enabled them to gain power and wealth through exclusive and restrictive corporate institutions

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

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc