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

Major ion and silicon isotope composition of glacial meltwaters, Leverett and Kiattuut glacier, Greenland

This data product contains dissolved and amorphous particulate silicon concentrations and isotopic compositions, and ancillary data (discharge, conductivity, suspended particulate matter, pH, major ion data) for glacial meltwaters collected from two glaciers in Greenland: Leverett Glacier (67 degrees N, 50 degrees W) and Kiattuut Sermiat (61 degrees N, 45 degrees W)

Silicon isotopic composition of dry and wet-based glaciers in Antarctica

Glaciers and ice sheets export significant amounts of silicon (Si) to downstream ecosystems, impacting local and potentially global biogeochemical cycles. Recent studies have shown Si in Arctic glacial meltwaters to have an isotopically distinct signature when compared to non-glacial rivers. This is likely linked to subglacial weathering processes and mechanochemical reactions. However, there are currently no silicon isotope (δ30Si) data available from meltwater streams in Antarctica, limiting the current inferences on global glacial silicon isotopic composition and its drivers. To address this gap, we present dissolved silicon (DSi), δ30SiDSi and major ion data from meltwater streams draining a polythermal glacier in the region of the West Antarctic peninsula (King George Island) and a cold-based glacier in East Antarctica (Commonwealth Stream, McMurdo Dry Valleys). These data, alongside other global datasets, improve our understanding of how contrasting glacier thermal regime can impact upon Si cycling and therefore the δ30SiDSi composition. We find a similar δ30SiDSi composition between the two sites, with the streams on King George Island varying between -0.23 and +1.23‰ and the Commonwealth stream varying from -0.40 to +1.14‰. However, meltwater streams in King George Island have higher DSi concentrations, and the two glacial systems exhibit opposite DSi - δ30SiDSi trends. These contrasts likely result from differences in weathering processes, specifically the role of subglacial processes (King George Island) and, supraglacial processes followed by in-stream weathering in hyporheic zones (Commonwealth Stream). These findings are important when considering likely changes in nutrient fluxes from Antarctic glaciers under climatic warming scenarios and consequent shifts in glacial thermal regimes

Biogeochemical and Silicon Isotopic Data for Dry and Wet-based Glaciers in Antarctica

This data product contains dissolved silicon concentrations and isotopic composition, major ion concentrations and discharge for streams in Potter Peninsula, King George Island and Commonwealth Stream, McMurdo Dry Valleys, Antarctica

Silicon Isotopic Composition of Dry and Wet-Based Glaciers in Antarctica

Glaciers and ice sheets export significant amounts of silicon (Si) to downstream ecosystems, impacting local and potentially global biogeochemical cycles. Recent studies have shown Si in Arctic glacial meltwaters to have an isotopically distinct signature when compared to non-glacial rivers. This is likely linked to subglacial weathering processes and mechanochemical reactions. However, there are currently no silicon isotope (d30Si) data available from meltwater streams in Antarctica, limiting the current inferences on global glacial silicon isotopic composition and its drivers. To address this gap, we present dissolved silicon (DSi), d30SiDSi, and major ion data from meltwater streams draining a polythermal glacier in the region of the West Antarctic Peninsula (WAP; King George Island) and a cold-based glacier in East Antarctica [Commonwealth Stream, McMurdo Dry Valleys (MDV)]. These data, alongside other global datasets, improve our understanding of how contrasting glacier thermal regime can impact upon Si cycling and therefore the d30SiDSi composition. We find a similar d30SiDSi composition between the two sites, with the streams on King George Island varying between -0.23 and C1.23h and the Commonwealth stream varying from - 0.40 to C1.14h. However, meltwater streams in King George Island have higher DSi concentrations, and the two glacial systems exhibit opposite DSi – d30SiDSi trends. These contrasts likely result from differences in weathering processes, specifically the role of subglacial processes (King George Island) and, supraglacial processes followed by in-stream weathering in hyporheic zones (Commonwealth Stream). These findings are important when considering likely changes in nutrient fluxes from Antarctic glaciers under climatic warming scenarios and consequent shifts in glacial thermal regimes

The silicon cycle impacted by past ice sheets.

Globally averaged riverine silicon (Si) concentrations and isotope composition (δ30Si) may be affected by the expansion and retreat of large ice sheets during glacial-interglacial cycles. Here we provide evidence of this based on the δ30Si composition of meltwater runoff from a Greenland Ice Sheet catchment. Glacier runoff has the lightest δ30Si measured in running waters (-0.25 ± 0.12‰), significantly lower than nonglacial rivers (1.25 ± 0.68‰), such that the overall decline in glacial runoff since the Last Glacial Maximum (LGM) may explain 0.06-0.17‰ of the observed ocean δ30Si rise (0.5-1.0‰). A marine sediment core proximal to Iceland provides further evidence for transient, low-δ30Si meltwater pulses during glacial termination. Diatom Si uptake during the LGM was likely similar to present day due to an expanded Si inventory, which raises the possibility of a feedback between ice sheet expansion, enhanced Si export to the ocean and reduced CO2 concentration in the atmosphere, because of the importance of diatoms in the biological carbon pump

Arts and Craft in Occupational Therapy (Activity Analysis)

Ergoterapie je profese, která se snaží o dosažení co největší soběstačnosti a samostatnosti jedince. Působí ve třech oblastech: soběstačnost, práce a produktivní aktivity a volnočasové činnosti. Historie ergoterapie sahá do 18. století, ale již i v době před naším letopočtem se vědělo o příznivém vlivu smysluplné činnosti v podobě práce či výtvarných a rukodělných činností. V České republice se začátek využití činnosti jako léčebného prostředku připisuje Priessnitzovi. V době komunismu ergoterapie nebyla potřebná a tak novou éru ergoterapie v České republice je možné datovat až od roku 1992. Pro ergoterapeuty je zásadní nástroj léčby činnost, lépe řečeno, smysluplná činnost. O významu činnosti pro ergoterapeuty psal již v roce 1922 AdolfMeyer. Vývoj ergoterapie je spjat s využíváním výtvarných a rukodělných činností. Jejich využívání se v průběhu vývoje společnosti, který ergoterapie reflektuje, snižuje, ale v Čechách je v jejich využívání stále silná tradice. Mezi důležité nástroje ergoterapeuta patří analýza činnosti, která pomáhá za prvé porozumět základní charakteristice jakékoliv činnosti. Za druhé pomáhá porozumět jedinci v co nejširším kontextu. Výsledkem použití analýzy činnosti je zvolení vhodné terapeutické činnosti pro konkrétního klienta, včetně navržení potřebných úprav pomůcek či..