Discharge Disposition and Loss of Independence Among Survivors of COVID-19 Admitted to Intensive Care: Results From the SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS).

OBJECTIVES: To describe incidence and risk factors of loss of previous independent living through nonhome discharge or discharge home with health assistance in survivors of intensive care unit (ICU) admission for coronavirus disease 2019 (COVID-19). DESIGN: Multicenter observational study including patients admitted to the ICU from January 2020 till June 30, 2021. HYPOTHESIS: We hypothesized that there is a high risk of nonhome discharge in patients surviving ICU admission due to COVID-19. SETTING: Data were included from 306 hospitals in 28 countries participating in the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 registry. PATIENTS: Previously independently living adult ICU survivors of COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was nonhome discharge. Secondary outcome was the requirement of health assistance among patients who were discharged home. Out of 10 820 patients, 7101 (66%) were discharged alive; 3791 (53%) of these survivors lost their previous independent living status, out of those 2071 (29%) through nonhome discharge, and 1720 (24%) through discharge home requiring health assistance. In adjusted analyses, loss of independence on discharge among survivors was predicted by patient age ≥ 65 years (adjusted odds ratio [aOR] 2.78, 95% confidence interval [CI] 2.47-3.14, P < .0001), former and current smoking status (aOR 1.25, 95% CI 1.08-1.46, P = .003 and 1.60 (95% CI 1.18-2.16), P = .003, respectively), substance use disorder (aOR 1.52, 95% CI 1.12-2.06, P = .007), requirement for mechanical ventilation (aOR 4.17, 95% CI 3.69-4.71, P < .0001), prone positioning (aOR 1.19, 95% CI 1.03-1.38, P = .02), and requirement for extracorporeal membrane oxygenation (aOR 2.28, 95% CI 1.55-3.34, P < .0001). CONCLUSIONS: More than half of ICU survivors hospitalized for COVID-19 are unable to return to independent living status, thereby imposing a significant secondary strain on health care systems worldwide.

Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children.

Importance: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C). Objective: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence. Design, Setting, and Participants: This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry. Exposure: Administration of steroids within 2 days of admission. Main Outcomes and Measures: Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching. Results: A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators. Conclusions and Relevance: Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients With COVID-19.

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

Quantifying the statistical power of monitoring programs for marine protected areas.

Marine Protected Areas (MPAs) are increasingly established globally as a spatial management tool to aid in conservation and fisheries management objectives. Assessing whether MPAs are having the desired effects on populations requires effective monitoring programs. A cornerstone of an effective monitoring program is an assessment of the statistical power of sampling designs to detect changes when they occur. We present a novel approach to power assessment that combines spatial point process models, integral projection models (IPMs) and sampling simulations to assess the power of different sample designs across a network of MPAs. We focus on the use of remotely operated vehicle (ROV) video cameras as the sampling method, though the results could be extended to other sampling methods. We use empirical data from baseline surveys of an example indicator fish species across three MPAs in California, USA as a case study. Spatial models simulated time series of spatial distributions across sites that accounted for the effects of environmental covariates, while IPMs simulated expected trends over time in abundances and sizes of fish. We tested the power of different levels of sampling effort (i.e., the number of 500-m ROV transects) and temporal replication (every 1-3 yr) to detect expected post-MPA changes in fish abundance and biomass. We found that changes in biomass are detectable earlier than changes in abundance. We also found that detectability of MPA effects was higher in sites with higher initial densities. Increasing the sampling effort had a greater effect than increasing sampling frequency on the time taken to achieve high power. High power was best achieved by combining data from multiple sites. Our approach provides a powerful tool to explore the interaction between sampling effort, spatial distributions, population dynamics, and metrics for detecting change in previously fished populations.

Monitoring the resilience of a no-take marine reserve to a range extending species using benthic imagery.

Global climate change is driving the redistribution of marine species and thereby potentially restructuring endemic communities. Understanding how localised conservation measures such as protection from additional human pressures can confer resilience to ecosystems is therefore an important area of research. Here, we examine the resilience of a no-take marine reserve (NTR) to the establishment of urchin barrens habitat. The barrens habitat is created through overgrazing of kelp by an invading urchin species that is expanding its range within a hotspot of rapid climate change. In our study region, a multi-year monitoring program provides a unique time-series of benthic imagery collected by an Autonomous Underwater Vehicle (AUV) within an NTR and nearby reference areas. We use a Bayesian hierarchical spatio-temporal modelling approach to estimate whether the NTR is associated with reduced formation of urchin barrens, and thereby enhances local resilience. Our approach controls for the important environmental covariates of depth and habitat complexity (quantified as rugosity derived from multibeam sonar mapping), as well as spatial and temporal dependence. We find evidence for the NTR conferring resilience with a strong reserve effect that suggests improved resistance to the establishment of barrens. However, we find a concerning and consistent trajectory of increasing barrens cover in both the reference areas and the NTR, with the odds of barrens increasing by approximately 32% per year. Thus, whereas the reserve is demonstrating resilience to the initial establishment of barrens, there is currently no evidence of recovery once barrens are established. We also find that depth and rugosity covariates derived from multibeam mapping provide useful predictors for barrens occurrence. These results have important management implications as they demonstrate: (i) the importance of monitoring programs to inform adaptive management; (ii) that NTRs provide a potential local conservation management tool under climate change impacts, and (iii) that technologies such as AUVs and multibeam mapping can be harnessed to inform regional decision-making. Continuation of the current monitoring program is required to assess whether the NTR can provide long term protection from a phase shift that replaces kelp with urchin barrens.

Closed-loop optimization of fast-charging protocols for batteries with machine learning.

Simultaneously optimizing many design parameters in time-consuming experiments causes bottlenecks in a broad range of scientific and engineering disciplines1,2. One such example is process and control optimization for lithium-ion batteries during materials selection, cell manufacturing and operation. A typical objective is to maximize battery lifetime; however, conducting even a single experiment to evaluate lifetime can take months to years3-5. Furthermore, both large parameter spaces and high sampling variability3,6,7 necessitate a large number of experiments. Hence, the key challenge is to reduce both the number and the duration of the experiments required. Here we develop and demonstrate a machine learning methodology  to efficiently optimize a parameter space specifying the current and voltage profiles of six-step, ten-minute fast-charging protocols for maximizing battery cycle life, which can alleviate range anxiety for electric-vehicle users8,9. We combine two key elements to reduce the optimization cost: an early-prediction model5, which reduces the time per experiment by predicting the final cycle life using data from the first few cycles, and a Bayesian optimization algorithm10,11, which reduces the number of experiments by balancing exploration and exploitation to efficiently probe the parameter space of charging protocols. Using this methodology, we rapidly identify high-cycle-life charging protocols among 224 candidates in 16 days (compared with over 500 days using exhaustive search without early prediction), and subsequently validate the accuracy and efficiency of our optimization approach. Our closed-loop methodology automatically incorporates feedback from past experiments to inform future decisions and can be generalized to other applications in battery design and, more broadly, other scientific domains that involve time-intensive experiments and multi-dimensional design spaces.

Redox-Dependent Metal-Metal Bonding in Trinuclear Metal Chains: Probing the Transition from Covalent Bonding to Exchange Coupling.

The synthesis and physical properties of two new cationic tri-metallic chains, [(PEt3 )3 RuCl3 M'Cl3 Ru(PEt3 )3 ]1+ , M'=Rh and Ir are reported. These are isostructural with a previously reported 17-electron all-ruthenium analogue, but replacing a d5 RuIII ion in the central position with d6 RhIII /IrIII has a significant impact on the nature of the metal-metal interactions. All three materials have been characterized electrochemically at the 18-, 17- and 16-electron levels. X-ray crystallography and spectroelectrochemistry, complemented by electronic structure analysis at the DFT and CASPT2 levels, indicate that whilst the presence of a RuIII ion in the center of the chain allows multi-center covalent bonding to develop, a closed-shell RhIII /IrIII ion pushes the system towards the exchange-coupled limit, where the outer Ru centers are only weakly interacting. This family of three isostructural compounds reveals how changes in metal composition can have subtle effects on physical properties of systems that lie close to the localized/delocalized borderline.

Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells.

Inflammatory cells and their mediators are known to contribute to neuropathic pain following nerve injury. Mast cells play a key role in non-neural models of inflammation and we propose that mast cells and their mediators (in particular histamine) are important in the development of neuropathic pain. In rats, where the sciatic nerve was partially ligated, we showed that stabilisation of mast cells with sodium cromoglycate reduced the recruitment of neutrophils and monocytes to the injured nerve and suppressed the development of hyperalgesia. Treatment with histamine receptor antagonists suppressed the development of hyperalgesia following nerve injury and alleviated hyperalgesia once it was established. These results suggest that mast cell mediators such as histamine released within hours of nerve injury contribute to the recruitment of leukocytes and the development of hyperalgesia.