Comment on Rishu et al. Time required to initiate outbreak and pandemic observational research

We applaud the work of Rishu and colleagues in tracking the timelines to initiation of outbreak and pandemic observational research. Through this work they highlight the challenges in being prepared with a clinical research response in the next pandemic. Pandemics are unpredictable but also recurrent. Recent experience of Ebola and Zika outbreaks highlight the devastating impact these outbreaks have on the health, economy and security of communities for generations to come

Species-Level Classification of Peatland Vegetation Using Ultra-High-Resolution UAV Imagery

Peatland restoration projects are being employed worldwide as a form of climate change mitigation due to their potential for long-term carbon sequestration. Monitoring these environments (e.g., cover of keystone species) is therefore essential to evaluate success. However, existing studies have rarely examined peatland vegetation at fine scales due to its strong spatial heterogeneity and seasonal canopy development. The present study collected centimetre-scale multispectral Uncrewed Aerial Vehicle (UAV) imagery with a Parrot Sequoia camera (2.8 cm resolution; Parrot Drones SAS, Paris, France) in a temperate peatland over a complete growing season. Supervised classification algorithms were used to map the vegetation at the single-species level, and the Maximum Likelihood classifier was found to perform best at the site level (69% overall accuracy). The classification accuracy increased with the spatial resolution of the input data, and a large reduction in accuracy was observed when employing imagery of >11 cm resolution. Finally, the most accurate classifications were produced using imagery collected during the peak (July–August) or early growing season (start of May). These findings suggest that despite the strong heterogeneity of peatlands, these environments can be mapped at the species level using UAVs. Such an approach would benefit studies estimating peatland carbon emissions or using the cover of keystone species to evaluate restoration projects

Hypercapnic Acidosis Reduces Oxidative Reactions in Endotoxin-Induced Lung Injury

Hypercapnic acidosis frequently occurs when patients with acute lung injury are initially ventilated with low tidal volume protective strategies. Hypercapnic acidosis per se, in the absence of any change in tidal volume or airway pressure, is protective when instituted before the onset of injury. However, the mechanisms by which hypercapnic acidosis confers this protection are incompletely understood, in particular, the effects on pulmonary oxidative reactions, which are potent mediators of tissue damage, have not been previously examined in vivo

Markovnikov-Selective, Activator-Free Iron-Catalyzed Vinylarene Hydroboration

Two series of structurally related alkoxy-tethered NHC iron­(II) complexes have been developed as catalysts for the regioselective hydroboration of alkenes. Significantly, Markonikov-selective alkene hydroboration with HBpin has been controllably achieved using an iron catalyst (11 examples, 35–90% isolated yield) with up to 37:1 branched:linear selectivity. <i>anti</i>-Markovnikov-selective alkene hydroboration was also achieved using HBcat and modification of the ligand backbone (6 examples, 44–71% yields). In both cases, ligand design has enabled activator-free low-oxidation-state iron catalysis

In‐Depth Extracorporeal Cardiopulmonary Resuscitation in Adult Out‐of‐Hospital Cardiac Arrest

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Dynamic lactate indices as predictors of outcome in critically ill patients

INTRODUCTION: Dynamic changes in lactate concentrations in the critically ill may predict patient outcome more accurately than static indices. We aimed to compare the predictive value of dynamic indices of lactatemia in the first 24 hours of intensive care unit (ICU) admission with the value of more commonly used static indices. METHODS: This was a retrospective observational study of a prospectively obtained intensive care database of 5,041 consecutive critically ill patients from four Australian university hospitals. We assessed the relationship between dynamic lactate values collected in the first 24 hours of ICU admission and both ICU and hospital mortality. RESULTS: We obtained 36,673 lactate measurements in 5,041 patients in the first 24 hours of ICU admission. Both the time weighted average lactate (LACTW₂₄) and the change in lactate (LACΔ₂₄) over the first 24 hours were independently predictive of hospital mortality with both relationships appearing to be linear in nature. For every one unit increase in LACTW₂₄ and LACΔ₂₄ the risk of hospital death increased by 37% (OR 1.37, 1.29 to 1.45; P < 0.0001) and by 15% (OR 1.15, 1.10 to 1.20; P < 0.0001) respectively. Such dynamic indices, when combined with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, improved overall outcome prediction (P < 0.0001) achieving almost 90% accuracy. When all lactate measures in the first 24 hours were considered, the combination of LACTW₂₄ and LACΔ₂₄ significantly outperformed (P < 0.0001) static indices of lactate concentration, such as admission lactate, maximum lactate and minimum lactate. CONCLUSIONS: In the first 24 hours following ICU admission, dynamic indices of hyperlactatemia have significant independent predictive value, improve the performance of illness severity score-based outcome predictions and are superior to simple static indices of lactate concentration

Arterial hyperoxia and in-hospital mortality after resuscitation from cardiac arrest

Introduction: Hyperoxia has recently been reported as an independent risk factor for mortality in patients resuscitated from cardiac arrest. We examined the independent relationship between hyperoxia and outcomes in such patients.Methods: We divided patients resuscitated from nontraumatic cardiac arrest from 125 intensive care units (ICUs) into three groups according to worst PaOlevel or alveolar-arterial Ogradient in the first 24 hours after admission. We defined 'hyperoxia' as PaOof 300 mmHg or greater, 'hypoxia/poor Otransfer' as either PaO 400 mmHg, hyperoxia had no independent association with mortality. Importantly, after adjustment for FiOand the relevant covariates, PaOwas no longer predictive of hospital mortality (P = 0.21).Conclusions: Among patients admitted to the ICU after cardiac arrest, hyperoxia did not have a robust or consistently reproducible association with mortality. We urge caution in implementing policies of deliberate decreases in FiOin these patients

Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study

INTRODUCTION: Higher lactate concentrations within the normal reference range (relative hyperlactatemia) are not considered clinically significant. We tested the hypothesis that relative hyperlactatemia is independently associated with an increased risk of hospital death. METHODS: This observational study examined a prospectively obtained intensive care database of 7,155 consecutive critically ill patients admitted to the Intensive Care Units (ICUs) of four Australian university hospitals. We assessed the relationship between ICU admission lactate, maximal lactate and time-weighted lactate levels and hospital outcome in all patients and also in those patients whose lactate concentrations (admission n = 3,964, maximal n = 2,511, and time-weighted n = 4,584) were under 2 mmol.L-1 (i.e. relative hyperlactatemia). RESULTS: We obtained 172,723 lactate measurements. Higher admission and time-weightedlactate concentration within the reference range was independently associated with increased hospital mortality (admission odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5, P = 0.01; time-weighted OR 3.7, 95% CI 1.9 to 7.00, P 0.75 mmol.L-1. Furthermore, in patients whose lactate ever exceeded 2 mmol.L-1, higher time-weighted lactate remained strongly associated with higher hospital mortality (OR 4.8, 95% CI 1.8 to 12.4, P 0.75 mmol.L-1 can be used by clinicians to identify patients at higher risk of death. The current reference range for lactate in the critically ill may need to be re-assessed

Venous thromboembolic events in critically ill traumatic brain injury patients

To estimate the prevalence, risk factors, prophylactic treatment and impact on mortality for venous thromboembolism (VTE) in patients with moderate to severe traumatic brain injury (TBI) treated in the intensive care unit. A post hoc analysis of the erythropoietin in traumatic brain injury (EPO-TBI) trial that included twice-weekly lower limb ultrasound screening. Venous thrombotic events were defined as ultrasound-proven proximal deep venous thrombosis (DVT) or clinically detected pulmonary embolism (PE). Results are reported as events, percentages or medians and interquartile range (IQR). Cox regression analysis was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to VTE and death. Of 603 patients, 119 (19.7%) developed VTE, mostly comprising DVT (102 patients, 16.9%) with a smaller number of PE events (24 patients, 4.0%). Median time to DVT diagnosis was 6 days (IQR 2-11) and to PE diagnosis 6.5 days (IQR 2-16.5). Mechanical prophylaxis (MP) was used in 91% of patients on day 1, 97% of patients on day 3 and 98% of patients on day 7. Pharmacological prophylaxis was given in 5% of patients on day 1, 30% of patients on day 3 and 57% of patients on day 7. Factors associated with time to VTE were age (HR per year 1.02, 95% CI 1.01-1.03), patient weight (HR per kg 1.01, 95% CI 1-1.02) and TBI severity according to the International Mission for Prognosis and Analysis of Clinical Trials risk of poor outcome (HR per 10% increase 1.12, 95% CI 1.01-1.25). The development of VTE was not associated with mortality (HR 0.92, 95% CI 0.51-1.65). Despite mechanical and pharmacological prophylaxis, VTE occurs in one out of every five patients with TBI treated in the ICU. Higher age, greater weight and greater severity of TBI increase the risk. The development of VTE was not associated with excess mortality.Peer reviewe

Cause and Timing of Death and Subgroup Differential Effects of Erythropoietin in the EPO-TBI Study

The EPO-TBI study randomized 606 patients with moderate or severe traumatic brain injury (TBI) to be treated with weekly epoetin alfa (EPO) or placebo. Six month mortality was lower in EPO treated patients in an analysis adjusting for TBI severity. Knowledge of possible differential effects by TBI injury subtype and acute neurosurgical treatment as well as timing and cause of death (COD) will facilitate the design of future interventional TBI trials. We defined COD as cerebral (brain death, cerebral death with withdrawal, or death during maximal care) and non-cerebral (death following withdrawal or during maximal care, which had a non-cerebral cause). The study included 305 patients treated with EPO and 297 treated with placebo, with COD recorded in 77 (99%) out of 78 non-survivors. Median time to death in patients dying of cerebral COD was 8 days (interquartile range [IQR] 5-16) compared with 29 days (IQR 7-56) (p = 0.01) for non-cerebral COD. When assessing subgroups by admission CT scan injury findings, we found no significant differential effects of EPO compared with placebo. However, EPO appeared more effective in patients with an injury type not requiring a neurosurgical operation prior to intensive care unit (ICU) admission (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.14-0.61, p = 0.001, p for interaction = 0.003) and in this subgroup, fewer patients died of cerebral causes in the EPO than in the placebo group (5% compared with 14%, p = 0.03). In conclusion, most TBI deaths were from cerebral causes that occurred during the first 2 weeks, and were related to withdrawal of care. EPO appeared to specifically reduce cerebral deaths in the important subgroup of patients with a diffuse type of injury not requiring a neurosurgical intervention prior to randomization.Peer reviewe