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

Effects of Compost and Organic Amendments on Weed Control

Using compost and soil amendments is beneficial to Florida citrus groves. Given the sandy nature of Florida soils and their low organic matter and cation exchange capacity (CEC), adding compost and organic amendments (e.g., humic acid) can enhance the ability of soil to retain water and nutrients. These practices can also boost soil microbial activity and improve soil health. Previous research has shown that yield losses from huanglongbing (HLB) affected trees correlate with low fibrous root densities and reduced root system capacity for water and nutrient uptake. Compost and organic amendments can thus aid citrus growers by improving overall soil physical, chemical, and biological properties. However, any strategies to boost tree growth can also potentially boost weed growth. So it is essential to understand the impacts of these soil management practices on weed emergence and infestation in citrus groves

Weed Management Strategies for Tomato Plasticulture Production in Florida

Florida is the top producer of fresh market tomatoes in the U.S., with an average production of 0.4 million metric tons. Tomatoes are commercially grown on plastic mulched raised beds in Southwest Florida, the primary production region in the state. Low tomato yield in plasticulture production is often associated with the poor control of nutsedge species. Nutsedge management, therefore, remains a critical production challenge for tomato growers in Florida. Sandy soil in this region promotes herbicide movement after heavy rainfall or irrigation, affecting weed suppression. This will also potentially impact the timely establishment of new tomato transplants and, consequently, the crop vigor if the herbicides get into the root zone. This review aims to present and discuss an overview of available options to safely manage major weeds of tomatoes, including nutsedge species, in plasticulture production. In addition, this review seeks to discuss an approach for utilizing herbicide adjuvants, such as spray deposition agents or oil binding agents, to improve herbicides’ efficacy and tomato crop safety by enhancing their retention in plastic mulched raised beds

New Advancements in Herbicide Spraying

Chemical weed control using herbicides is essential for profitable citrus production as it reduces the competition from weeds. This article explores the use of herbicide spraying technologies, such as using sensors and artificial intelligence to increase herbicide use efficiency and eliminate negative environmental impacts

Survival and Feeding Behavior of <i>Diaphorina citri</i> (Hemiptera: Liviidae) Adults on Common Cover Crops in Citrus

Asian citrus psyllid, Diaphorina citri, transmits Candidatus Liberibacter asiaticus (CLas), the bacterial pathogen responsible for citrus greening disease. To explore the possibility that cover crops in citrus groves may serve as refuges for this pathogen vector during unfavorable host conditions, psyllid feeding was investigated on six common cover crop species and citrus using electrical penetration graph (EPG) recordings and behavioral bioassays. EPG recordings showed that the proportion of time spent by D. citri feeding on xylem was similar or higher on all tested cover crops (17%–32%) compared to the positive control (12%), the preferred host, Citrus macrophylla. Very little to no phloem feeding was observed on cover crops by the adults. In the choice assays, more D. citri adults settled on buckwheat (Fagopyrum esculentum) and cowpea (Vigna unguiculata) than on the host, C. macrophylla, 24 h after release. No-choice assays showed that the citrus cover crop species evaluated extend the survival of D. citri up to 8 d because of xylem feeding. Our results indicate that some cover crop species may be less suitable refuge sites for D. citri than others, but none served as breeding sites or supported more than 8 d of survival