Your supervisor’s personality impacts you forever

Supervisors are different in their managerial abilities and in how they perceive your work, yet their decisions determine you career outcomes, write Anders Frederiksen, Lisa Kahn, and Fabian Lang

Lower <i>versus</i> higher oxygenation targets in critically ill patients with severe hypoxaemia:secondary Bayesian analysis to explore heterogeneous treatment effects in the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial

BACKGROUND: In the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial, a lower (8 kPa) vs a higher (12 kPa) PaO(2) target did not affect mortality amongst critically ill adult patients. We used Bayesian statistics to evaluate any heterogeneity in the effect of oxygenation targets on mortality between different patient groups within the HOT-ICU trial. METHODS: We analysed 90-day all-cause mortality using adjusted Bayesian logistic regression models, and assessed heterogeneous treatment effects according to four selected baseline variables using both hierarchical models of subgroups and models with interactions on the continuous scales. Results are presented as mortality probability (%) and relative risk (RR) with 95% credibility intervals (CrI). RESULTS: All 2888 patients in the intention-to-treat cohort of the HOT-ICU trial were included. The adjusted 90-day mortality rates were 43.0% (CrI: 38.3–47.8%) and 42.3% (CrI: 37.7–47.1%) in the lower and higher oxygenation groups, respectively (RR 1.02 [CrI: 0.93–1.11]), with 36.5% probability of an RR <1.00. Analyses of heterogeneous treatment effects suggested a dose–response relationship between baseline norepinephrine dose and increased mortality with the lower oxygenation target, with 95% probability of increased mortality associated with the lower oxygenation target as norepinephrine doses increased. CONCLUSIONS: A lower oxygenation target was unlikely to affect overall mortality amongst critically ill adult patients with acute hypoxaemic respiratory failure. However, our results suggest an increasing mortality risk for patients with a lower oxygen target as the baseline norepinephrine dose increases. These findings warrant additional investigation. CLINICAL TRIAL REGISTRATION: NCT03174002

The economically optimal warming limit of the planet

Both climate-change damages and climate-change mitigation will incur economic costs. While the risk of severe damages increases with the level of global warming (Dell et al., 2014; IPCC, 2014b, 2018; Lenton et al., 2008), mitigating costs increase steeply with more stringent warming limits (IPCC, 2014a; Luderer et al., 2013; Rogelj et al., 2015). Here, we show that the global warming limit that minimizes this century's total economic costs of climate change lies between 1.9 and 2°C, if temperature changes continue to impact national economic growth rates as observed in the past and if instantaneous growth effects are neither compensated nor amplified by additional growth effects in the following years. The result is robust across a wide range of normative assumptions on the valuation of future welfare and inequality aversion. We combine estimates of climate-change impacts on economic growth for 186 countries (applying an empirical damage function from Burke et al., 2015) with mitigation costs derived from a state-of-the-art energy-economy-climate model with a wide range of highly resolved mitigation options (Kriegler et al., 2017; Luderer et al., 2013, 2015). Our purely economic assessment, even though it omits non-market damages, provides support for the international Paris Agreement on climate change. The political goal of limiting global warming to "well below 2 degrees" is thus also an economically optimal goal given above assumptions on adaptation and damage persistence. © 2019 Copernicus GmbH. All rights reserved

Associations between enteral nutrition and outcomes in the SUP ‐ ICU trial: Results of exploratory post hoc analyses

Background: Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions between enteral nutrition and pantoprazole. Methods: Extended Cox models with time‐varying co‐variates and competing events were used to assess potential associations, adjusted for baseline severity of illness. Potential interactions between daily enteral nutrition and allocation to pantoprazole on outcomes were similarly assessed. Results: Enteral nutrition was associated with lower risk of clinically important gastrointestinal bleeding (cause‐specific hazard ratio [HR]: 0.29, 95% confidence interval: [CI] 0.19–0.44, p < .001), higher risk of pneumonia (HR: 1.44, 95% CI: 1.14–1.82, p = .003), and lower risk of all‐cause mortality (HR: 0.22, 95% CI: 0.18–0.27, p < .001). Enteral nutrition with allocation to pantoprazole was associated with a lower risk of mortality (HR: 0.27, 95% CI: 0.21–0.35, p < .001), similar to enteral nutrition with allocation to placebo (HR: 0.17, 95% CI: 0.13–0.23, p < .001). Allocation to pantoprazole with no enteral nutrition had little effect on mortality (HR: 0.83, 95% CI: 0.63–1.09, p = .179), whilst allocation to pantoprazole and receipt of enteral nutrition was mostly compatible with increased all‐cause mortality (HR: 1.27, 95% CI: 0.99–1.64, p = .061). The test of interaction between enteral nutrition and pantoprazole treatment allocation for all‐cause mortality was statistically significant (p = .024). Conclusions: Enteral nutrition was associated with an increased risk of pneumonia and a reduced risk of gastrointestinal bleeding. The interaction between pantoprazole and enteral nutrition suggesting an increased risk of mortality requires further study