| 1. |
- Munch, Marie W., et al.
(author)
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Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
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In: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
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Journal article (peer-reviewed)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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| 2. |
- Haahr, Thor, et al.
(author)
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Vaginal dysbiosis in pregnancy associates with risk of emergency caesarean section: a prospective cohort study
- 2022
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In: Clinical Microbiology and Infection. - Oxford, United Kingdom : Elsevier. - 1198-743X .- 1469-0691. ; 28:4, s. 588-595
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Journal article (peer-reviewed)abstract
- Objectives: To investigate changes in vaginal microbiota during pregnancy, and the association between vaginal dysbiosis and reproductive outcomes.Methods: A total of 730 (week 24) and 666 (week 36) vaginal samples from 738 unselected pregnant women were studied by microscopy (Nugent score) and characterized by 16S rRNA gene sequencing. A novel continuous vaginal dysbiosis score was developed based on these methods using a supervised partial least squares model.Results: Among women with bacterial vaginosis in week 24 (n = 53), 47% (n = 25) also had bacterial vaginosis in week 36. In contrast, among women without bacterial vaginosis in week 24, only 3% (n = 18) developed bacterial vaginosis in week 36. Vaginal samples dominated by Lactobacillus crispatus (OR 0.35, 95% CI 0.20–0.60) and Lactobacillus iners (OR 0.40, 95% CI 0.23–0.68) in week 24 were significantly more stable by week 36 when compared with other vaginal community state types. Vaginal dysbiosis score at week 24 was associated with a significant increased risk of emergency, but not elective, caesarean section (OR 1.37, 955 CI 1.15–1.64, p < 0.001), suggesting a 37% increased risk per standard deviation increase in vaginal dysbiosis score.Conclusions: Changes in vaginal microbiota from week 24 to week 36 of pregnancy correlated with bacterial vaginosis status and vaginal community state type. A novel vaginal dysbiosis score was associated with a significantly increased risk of emergency, but not elective, caesarean section. This was not found for bacterial vaginosis or any vaginal community state type and could point to the importance of investigating vaginal dysbiosis as a nuanced continuum instead of crude clusters.
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| 3. |
- Sen, Arunima, et al.
(author)
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The phylogeography and ecology of Oligobrachia frenulate species suggest a generalist chemosynthesis-based fauna in the arctic
- 2023
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In: Heliyon. - : Elsevier BV. - 2405-8440. ; 9:3
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Journal article (peer-reviewed)abstract
- We used ancient DNA (aDNA) extraction methods to sequence museum voucher samples of Oligobrachia webbi, a frenulate siboglinid polychaete described from a northern Norwegian fjord over fifty years ago. Our sequencing results indicate a genetic match with the cryptic seep species, Oligobrachia haakonmosbiensis (99% pairwise identity for 574 bp mtCOI fragments). Due to its similarity with O. webbi, the identity of O. haakonmosbiensis has been a matter of debate since its description, which we have now resolved. Furthermore, our results demonstrate that chemosynthesis-based siboglinids, that constitute the bulk of the biomass at Arctic seeps are not seep specialists. Our data on sediment geochemistry and carbon and nitrogen content reveal reduced conditions in fjords/sounds, similar to those at seep systems. Accumulation and decomposition of both terrestrial and marine organic matter results in the buildup of methane and sulfide that apparently can sustain chemosymbiotic fauna. The occurrence of fjords and by extension, highly reducing habitats, could have led to Arctic chemosymbiotic species being relatively generalist with their habitat, as opposed to being seep or vent specialists. Our stable isotope analyses indicate the incorporation of photosynthetically derived carbon in some individuals, which aligns with experiments conducted on frenulates before the discovery of chemosynthesis that demonstrated their ability to take up organic molecules from the surrounding sediment. Since reduced gases in non-seep environments are ultimately sourced from photosynthetic processes, we suggest that the extreme seasonality of the Arctic has resulted in Arctic chemosymbiotic animals seasonally changing their degree of reliance on chemosynthetic partners. Overall, the role of chemosynthesis in Arctic benthos and marine ecosystems and links to photosynthesis may be complex, and more extensive than currently known.
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