Prone position ventilation (PPV) is resource-intensive, yet the optimal strategy for PPV in intubated patients with COVID-19 is unclear.
Does a prolonged (24 or more h) PPV strategy improve mortality ...in intubated COVID-19 patients compared with intermittent (∼16 h with daily supination) PPV?
Multicenter, retrospective cohort study of consecutively admitted intubated COVID-19 patients treated with PPV between March 11 and May 31, 2020. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 90-day all-cause mortality and prone-related complications. Inverse probability treatment weights (IPTW) were used to control for potential treatment selection bias.
Of the COVID-19 patients who received PPV, 157 underwent prolonged and 110 underwent intermittent PPV. Patients undergoing prolonged PPV had reduced 30-day (adjusted hazard ratio aHR, 0.475; 95% CI, 0.336-0.670; P < .001) and 90-day (aHR, 0.638; 95% CI, 0.461-0.883; P = .006) mortality compared with intermittent PPV. In patients with Pao2/Fio2 ≤ 150 at the time of pronation, prolonged PPV was associated with reduced 30-day (aHR, 0.357; 95% CI, 0.213-0.597; P < .001) and 90-day mortality (aHR, 0.562; 95% CI, 0.357-0.884; P = .008). Patients treated with prolonged PPV underwent fewer pronation and supination events (median, 1; 95% CI, 1-2 vs 3; 95% CI, 1-4; P < .001). PPV strategy was not associated with overall PPV-related complications, although patients receiving prolonged PPV had increased rates of facial edema and lower rates of peri-proning hypotension.
Among intubated COVID-19 patients who received PPV, prolonged PPV was associated with reduced mortality. Prolonged PPV was associated with fewer pronation and supination events and a small increase in rates of facial edema. These findings suggest that prolonged PPV is a safe, effective strategy for mortality reduction in intubated COVID-19 patients.
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Code status orders impact clinical outcomes as well as patients’ and surrogates’ experiences. This is the first multicenter cohort examining code status orders of ICU patients with COVID-19 reported ...to date.
This is a retrospective cohort study including adult patients who tested positive for SARS-CoV-2 and were admitted to the ICU at three hospitals in Massachusetts from March 11, 2020 - May 31, 2020. We examined differences in code status orders at multiple timepoints and performed multivariable regression analysis to identify variables associated with code status at admission.
Among 459 ICU patients with COVID-19, 421 (91.7%) were Full Code at hospital admission. Age and admission from a facility were positively associated with DNR status (adjusted OR 1.10, 95% CI 1.05–1.15, p < 0.001 and adjusted OR 2.68, CI 1.23–5.71, p = 0.011, respectively) while non-English preferred language was negatively associated with DNR status (adjusted OR 0.29, 95% CI 0.10–0.74, p = 0.012). Among 147 patients who died during hospitalization, 95.2% (140) died with DNR code status; most (86.4%) died within two days of final code status change.
The association of non-English preferred language with Full Code status in critically ill COVID-19 patients highlights the importance of medical interpreters in the ICU. Patients who died were transitioned to DNR more than in previous studies, possibly reflecting changes in practice during a novel pandemic.
Which social factors explain racial and ethnic disparities in COVID-19 access to care and outcomes remain unclear.
We hypothesized that preferred language mediates the association between race, ...ethnicity and delays to care.
Multicenter, retrospective cohort study of adults with COVID-19 consecutively admitted to the ICU in three Massachusetts hospitals in 2020.
Causal mediation analysis was performed to evaluate potential mediators including preferred language, insurance status, and neighborhood characteristics.
Non-Hispanic White (NHW) patients (157/442, 36%) were more likely to speak English as their preferred language (78% vs. 13%), were less likely to be un- or under-insured (1% vs. 28%), lived in neighborhoods with lower social vulnerability index (SVI) than patients from racial and ethnic minority groups (SVI percentile 59 28 vs. 74 21) but had more comorbidities (Charlson comorbidity index 4.6 2.5 vs. 3.0 2.5), and were older (70 13.2 vs. 58 15.1 years). From symptom onset, NHW patients were admitted 1.67 0.71-2.63 days earlier than patients from racial and ethnic minority groups (
< 0.01). Non-English preferred language was associated with delay to admission of 1.29 0.40-2.18 days (
< 0.01). Preferred language mediated 63% of the total effect (
= 0.02) between race, ethnicity and days from symptom onset to hospital admission. Insurance status, social vulnerability, and distance to the hospital were not on the causal pathway between race, ethnicity and delay to admission.
Preferred language mediates the association between race, ethnicity and delays to presentation for critically ill patients with COVID-19, although our results are limited by possible collider stratification bias. Effective COVID-19 treatments require early diagnosis, and delays are associated with increased mortality. Further research on the role preferred language plays in racial and ethnic disparities may identify effective solutions for equitable care.
Shiga toxin (Stx)-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is the leading cause of acute kidney injury in children, with an associated mortality of up to 5%. The mechanisms ...underlying STEC-HUS and why the glomerular microvasculature is so susceptible to injury following systemic Stx infection are unclear.
Transgenic mice were engineered to express the Stx receptor (Gb3) exclusively in their kidney podocytes (Pod-Gb3) and challenged with systemic Stx. Human glomerular cell models and kidney biopsies from patients with STEC-HUS were also studied.
Stx-challenged Pod-Gb3 mice developed STEC-HUS. This was mediated by a reduction in podocyte vascular endothelial growth factor A (VEGF-A), which led to loss of glomerular endothelial cell (GEnC) glycocalyx, a reduction in GEnC inhibitory complement factor H binding, and local activation of the complement pathway. Early therapeutic inhibition of the terminal complement pathway with a C5 inhibitor rescued this podocyte-driven, Stx-induced HUS phenotype.
This study potentially explains why systemic Stx exposure targets the glomerulus and supports the early use of terminal complement pathway inhibition in this devastating disease.
This work was supported by the UK Medical Research Council (MRC) (grant nos. G0901987 and MR/K010492/1) and Kidney Research UK (grant nos. TF_007_20151127, RP42/2012, and SP/FSGS1/2013). The Mary Lyon Center is part of the MRC Harwell Institute and is funded by the MRC (A410).
Experimental evidence points increasingly to the importance of posttranslational processes such as phosphorylation and translocation in the molecular circadian clocks of many organisms. We develop a ...mathematical model of the
Drosophila circadian clock that incorporates the emerging details of the timing of nuclear translocation of the PERIOD and TIMELESS proteins. Most models assume that these proteins enter the nucleus as a complex, but recent experiments suggest that they in fact enter the nucleus separately. Our model reproduces observed patterns of intracellular localization of PERIOD and TIMELESS during light–dark cycles and in constant darkness, as well as phenotypes of several clock mutants. We also use the model to demonstrate how the
Drosophila clock can exhibit robust oscillations with constant mRNA levels of
period or
timeless, and propose a possible mechanism for oscillations in double-rescue experiments of
per
01
–
tim
01
mutants. The model also explains (via posttranslational processes) the counter-intuitive observation that total dCLOCK levels are at their lowest at the circadian time when active nuclear dCLOCK must be peaking in order to activate transcription of other clock genes, implying that for dCLOCK a posttranslationally generated rhythm is more important than the transcriptionally generated rhythm. These results support the idea that posttranslational processes play key roles in generating as well as modulating robust circadian oscillations. While it appears that posttranslational mechanisms alone are not sufficient to generate rhythms in
Drosophila, posttranslational mechanisms can greatly amplify a very weak transcriptional rhythm.
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