Pulp, Vol. 4 No. 1

This is the fourth issue of Pulp.https://scholarworks.sfasu.edu/pulp/1003/thumbnail.jp

Pulp, Vol. 4 No. 1

This is the fourth issue of Pulp.https://scholarworks.sfasu.edu/pulp/1003/thumbnail.jp

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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 effects of burrow nesting seabirds on soil and vegetation on Broughton Island, New South Wales - Dataset

The research data generated for this thesis contains soil chemical data which was sampled from Broughton Island, New South Wales, Australia. Soils were analysed at the University of New England and Southern Cross University in New South Wales. The dataset was used to inform the research question how breeding seabirds affect the soil environment in terms of nutrient enrichment, carbon sequestration, and cycling of stable nitrogen and carbon isotopes. The data was used in chapters 3 and 4 in the thesis. Vegetation data used in chapter 5 was collected by the National Parks and Wildlife Service by surveying transect with plants and measuring species richness, plant cover, and height over several years of surveys

The Effects of Burrow Nesting Seabirds on Soils and Vegetation on Broughton Island, New South Wales

The offshore islands of New South Wales host millions of migratory seabirds that
 gather in dense colonies on islands to breed. Seabirds have the capacity to drive ecosystem
 function through dual roles of marine-derived nutrient subsidies via guano deposition and
 bioengineering through burrow-nesting. Broughton Island is managed as part of the Myall
 Lakes National Park estate and has experienced a range of environmental disturbances in the
 past decade including the introduction of invasive plants and mammals, which led to significant
 changes to seabird populations and native vegetation communities. In response to the threats
 imposed by grazing rabbits and predatory rats on seabird habitat and breeding success, these
 invasive animals were successfully eradicated from the island in 2009 with the goal of restoring
 seabird populations and plant communities. The trajectory of ecological change, however,
 remained largely unknown. The aims of the research presented in this thesis were to first gain
 scope on the effect of seabird nutrient subsidies and nesting activities on island soils and plants
 in colonies of the most abundant seabird species on the island, Ardenna pacifica (wedge-tailed
 shearwaters).
 The results revealed novel evidence of seabird colony soils more depleted in soil C, N
 and P compared to both adjacent and sloping areas of hydrological accumulation. It was also
 found that vegetation was distinctly different within seabird colonies and was defined by the
 presence of an invasive cactus, Opuntia stricta. This result will be the first to describe in detail
 how burrowing seabirds on islands with deep and sandy soils in a subtropical climate, affect
 their environment, thereby giving new insights onto the mechanisms driving ecosystem
 function and the management implications for such islands.
 Another key research aim was to elucidate the effectiveness of eradication of rats and
 rabbits was effective in restoring native vegetation cover and richness on Broughton Island by analysing data collected from 7 years of vegetation surveys. Overall positive effects were seen
 in vegetation height, species richness, and ground cover, but it may take successional plant
 communities longer time to recover and require additional interventions for optimal outcomes.
 It was concluded that positive outcomes of vegetation recovery may be confounded by areas
 with disturbance by burrowing seabirds, and was supported by the evidence supplied by the
 research comparing vegetation and soil characteristics inside and outside of seabird colonies.
 Two experimental habitat suitability models were created taking different but
 complementary approaches to predict preferred and projected colony habitat on Broughton
 Island. Both models had high accuracy at detecting suitable habitat on the island, and both
 models identified unoccupied areas of high habitat suitability which were used in conjunction
 with other results to make robust conclusions.
 Identifying the fundamental effects of seabirds on soils and plants in nesting areas
 provided evidence to predict how expanding seabird colonies may change the soil and
 vegetation environment on this distinctive island ecosystem. The spatial results, combined with
 the knowledge of biophysical effects on soils and vegetation from seabird colonies, identified
 precise areas which are predicted to experience change in vegetation and guano subsidies if
 seabird colonies should expand to these highly suitable areas. Since expansion of seabird
 colonies into suitable habitat is likely now Broughton Island is predator-free, the opportunity
 for effective biocontrol of weeds, and protection of habitat now exists. 
 This work demonstrates how multifaceted approach using field surveys, laboratory and
 geospatial analyses strengthen ecological conclusions and can be applied to effective and real world conservation plans on islands experiencing ecological changes. The results will be
 utilised by the New South Wales National Parks and Wildlife Service to inform future island
 management

An ecological study of the relationship between social and environmental determinants of obesity

There is growing concern with the increasing prevalence of obesity in industrialised countries, a trend that is more apparent in the poor than in the rich. In an ecological study, the relationship between an area measure of socioeconomic status (SES) and the density of fast-food outlets was examined as one possible explanation for the phenomenon. It was found that there was a dose-response between SES and the density of fast-food outlets, with people living in areas from the poorest SES category having 2.5 times the exposure to outlets than people in the wealthiest category. The findings are discussed.<br /