Fostering greater recognition of Caribbean traditional plant knowledge.

The Caribbean is a hotspot of biological and cultural diversity, manifested in traditional plant knowledge of Afrodescendant peoples and other ethnicities. To strengthen the visibility of this knowledge in research, education, and policy making, we propose an eight-step action plan centered on reciprocal relationships with Caribbean plant stewards, especially subsistence farmers.

Contrasting water-use strategies revealed by species-specific transpiration dynamics in the Caatinga dry forest.

In forest ecosystems, transpiration (T) patterns are important for quantifying water and carbon fluxes and are major factors in predicting ecosystem change. Seasonal changes in rainfall and soil water content can alter the sensitivity of sap flux density to daily variations in vapor pressure deficit (VPD). This sensitivity is species-specific and is thought to be related to hydraulic strategies. The aim of this work is to better understand how the sap flux density of species with low versus high wood density differ in their sensitivity to VPD and soil water content and how potentially opposing water-use strategies influence T dynamics, and ultimately, correlations to evapotranspiration (ET). We use hysteresis area analysis to quantify the sensitivity of species-specific sap flux density to changes in the VPD, breakpoint-based models to determine the soil water content threshold instigating a T response and multiscalar wavelet coherency to correlate T to ET. We found that low wood density Commiphora leptophloeos (Mart.) Gillett had a more dynamic T pattern, a greater sensitivity to VPD at high soil water content, required a higher soil water content threshold for this sensitivity to be apparent, and had a significant coherency correlation with ET at daily to monthly timescales. This behavior is consistent with a drought avoidance strategy. High wood density Cenostigma pyramidale  (Tul.)  E. Gagnon & G. P. Lewis, conversely, had a more stable T pattern, responded to VPD across a range of soil water content, tolerated a lower soil water content threshold to T, and had a significant coherency correlation with ET at weekly timescales. This behavior is consistent with a drought-tolerant strategy. We build on previous research to show that these species have contrasting water-use strategies that should be considered in large-scale modeling efforts.

Prophylactic Administration of Vasopressors Prior to Emergency Intubation in Critically Ill Patients: A Secondary Analysis of Two Multicenter Clinical Trials.

Hypotension affects approximately 40% of critically ill patients undergoing emergency intubation and is associated with an increased risk of death. The objective of this study was to examine the association between prophylactic vasopressor administration and the incidence of peri-intubation hypotension and other clinical outcomes. DESIGN: A secondary analysis of two multicenter randomized clinical trials. The clinical effect of prophylactic vasopressor administration was estimated using a one-to-one propensity-matched cohort of patients with and without prophylactic vasopressors. SETTING: Seven emergency departments and 17 ICUs across the United States. PATIENTS: One thousand seven hundred ninety-eight critically ill patients who underwent emergency intubation at the study sites between February 1, 2019, and May 24, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was peri-intubation hypotension defined as a systolic blood pressure less than 90 mm Hg occurring between induction and 2 minutes after tracheal intubation. A total of 187 patients (10%) received prophylactic vasopressors prior to intubation. Compared with patients who did not receive prophylactic vasopressors, those who did were older, had higher Acute Physiology and Chronic Health Evaluation II scores, were more likely to have a diagnosis of sepsis, had lower pre-induction systolic blood pressures, and were more likely to be on continuous vasopressor infusions prior to intubation. In our propensity-matched cohort, prophylactic vasopressor administration was not associated with reduced risk of peri-intubation hypotension (41% vs 32%; p = 0.08) or change in systolic blood pressure from baseline (-12 vs -11 mm Hg; p = 0.66). CONCLUSIONS: The administration of prophylactic vasopressors was not associated with a lower incidence of peri-intubation hypotension in our propensity-matched analysis. To address potential residual confounding, randomized clinical trials should examine the effect of prophylactic vasopressor administration on peri-intubation outcomes.

Peer support interventions in patients with kidney failure: A systematic review.

BACKGROUND: Peer support has been associated with improved health-related outcomes (e.g., psychological well-being and treatment adherence) among patients with serious, chronic conditions, including kidney disease. Yet, there is little existing research evaluating the effects of peer support programs on health outcomes among patients with kidney failure being treated with kidney replacement therapy. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we conducted a systematic review using five databases to assess the effects of peer support programs on health-related outcomes (e.g., physical symptoms, depression) among patients with kidney failure undergoing kidney replacement therapy. RESULTS: Peer support in kidney failure was assessed across 12 studies (eight randomized controlled trials, one quasi-experimental controlled trial, and three single-arm trials) with 2893 patients. Three studies highlighted the links between peer support and improved patient engagement with care, while one found peer support did not significantly impact engagement. Three studies showed associations between peer support and improvements in psychological well-being. Four studies underscored the effects of peer support on self-efficacy and one on treatment adherence. CONCLUSIONS: Despite preliminary evidence of the positive associations between peer support and health-related outcomes among patients with kidney failure, peer support programs for this patient population remain poorly understood and underutilized. Further rigorous prospective and randomized studies are needed to evaluate how peer support can be optimized and incorporated into clinical care for this vulnerable patient population.

Laryngoscopy and Tracheal Intubation: Does Use of a Video Laryngoscope Facilitate Both Steps of the Procedure?

STUDY OBJECTIVE: To compare the effect of the use of a video laryngoscope versus a direct laryngoscope on each step of emergency intubation: laryngoscopy (step 1) and intubation of the trachea (step 2). METHODS: In a secondary observational analysis of data from 2 multicenter, randomized trials that enrolled critically ill adults undergoing tracheal intubation but did not control for laryngoscope type (video laryngoscope vs direct laryngoscope), we fit mixed-effects logistic regression models examining the 1) the association between laryngoscope type (video laryngoscope vs direct laryngoscope) and the Cormack-Lehane grade of view and 2) the interaction between grade of view, laryngoscope type (video laryngoscope vs direct laryngoscope), and the incidence of successful intubation on the first attempt. RESULTS: We analyzed 1,786 patients: 467 (26.2%) in the direct laryngoscope group and 1,319 (73.9%) in the video laryngoscope group. The use of a video laryngoscope was associated with an improved grade of view as compared with a direct laryngoscope (adjusted odds ratio for increasingly favorable grade of view 3.14, 95% confidence interval [CI] 2.47 to 3.99). Successful intubation on the first attempt occurred in 83.2% of patients in the video laryngoscope group and 72.2% of patients in the direct laryngoscope group (absolute difference 11.1%, 95% CI 6.5% to 15.6%). Video laryngoscope use modified the association between grade of view and successful intubation on the first attempt such that intubation on the first attempt was similar between video laryngoscope and direct laryngoscope at a grade 1 view and higher for video laryngoscope than direct laryngoscope at grade 2 to 4 views (P<.001 for interaction term). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, the use of a video laryngoscope was associated both with a better view of the vocal cords and with a higher probability of successfully intubating the trachea when the view of the vocal cords was incomplete in this observational analysis. However, a multicenter, randomized trial directly comparing the effect of a video laryngoscope with a direct laryngoscope on the grade of view, success, and complications is needed.

Defining Successful Intubation on the First Attempt Using Both Laryngoscope and Endotracheal Tube Insertions: A Secondary Analysis of Clinical Trial Data.

STUDY OBJECTIVES: Successful intubation on the first attempt has historically been defined as successful placement of an endotracheal tube (ETT) using a single laryngoscope insertion. More recent studies have defined successful placement of an ETT using a single laryngoscope insertion followed by a single ETT insertion. We sought to estimate the prevalence of first-attempt success using these 2 definitions and estimate their associations with the duration of intubation and serious complications. METHODS: We performed a secondary analysis of data from 2 multicenter randomized trials of critically ill adults being intubated in the emergency department or ICU. We calculated the percent difference in successful intubations on the first attempt, median difference in the duration of intubation, and percent difference in the development of serious complications by definition. RESULTS: The study population included 1,863 patients. Successful intubation on the first attempt decreased by 4.9% (95% confidence interval 2.5% to 7.3%) when defined as 1 laryngoscope insertion followed by 1 ETT insertion (81.2%) compared with when defined as only 1 laryngoscope insertion (86.0%). When successful intubation with 1 laryngoscope and 1 ETT insertion was compared with 1 laryngoscope and multiple ETT insertions, the median duration of intubation decreased by 35.0 seconds (95% confidence interval 8.9 to 61.1 seconds). CONCLUSION: Defining successful intubation on the first attempt as placement of an ETT in the trachea using 1 laryngoscope and 1 ETT insertion identifies attempts with the shortest apneic time.

Individualized Treatment Effects of Bougie versus Stylet for Tracheal Intubation in Critical Illness.

Rationale: A recent randomized trial found that using a bougie did not increase the incidence of successful intubation on first attempt in critically ill adults. The average effect of treatment in a trial population, however, may differ from effects for individuals. Objective: We hypothesized that application of a machine learning model to data from a clinical trial could estimate the effect of treatment (bougie vs. stylet) for individual patients based on their baseline characteristics ("individualized treatment effects"). Methods: This was a secondary analysis of the BOUGIE (Bougie or Stylet in Patients Undergoing Intubation Emergently) trial. A causal forest algorithm was used to model differences in outcome probabilities by randomized group assignment (bougie vs. stylet) for each patient in the first half of the trial (training cohort). This model was used to predict individualized treatment effects for each patient in the second half (validation cohort). Measurements and Main Results: Of 1,102 patients in the BOUGIE trial, 558 (50.6%) were the training cohort, and 544 (49.4%) were the validation cohort. In the validation cohort, individualized treatment effects predicted by the model significantly modified the effect of trial group assignment on the primary outcome (P value for interaction = 0.02; adjusted qini coefficient, 2.46). The most important model variables were difficult airway characteristics, body mass index, and Acute Physiology and Chronic Health Evaluation II score. Conclusions: In this hypothesis-generating secondary analysis of a randomized trial with no average treatment effect and no treatment effect in any prespecified subgroups, a causal forest machine learning algorithm identified patients who appeared to benefit from the use of a bougie over a stylet and from the use of a stylet over a bougie using complex interactions between baseline patient and operator characteristics.

Effect of Laryngoscope Blade Size on First Pass Success of Tracheal Intubation in Critically Ill Adults.

Tracheal intubation (TI) is a common procedure in critical care, often performed with a Macintosh curved blade used for direct laryngoscopy (DL). Minimal evidence informs the choice between Macintosh blade sizes during TI. We hypothesized that Macintosh 4 blade would have higher first-attempt success than Macintosh 3 blade during DL. DESIGN: Retrospective analysis using a propensity score and inverse probability weighting of data from six prior multicenter randomized trials. SETTING AND PARTICIPANTS: Adult patients who underwent nonelective TI at participating emergency departments and ICUs. We compared the first-pass success of TI with DL in subjects intubated with a size 4 Macintosh blade on the first TI attempt to subjects with a size 3 Macintosh blade on the first TI attempt. MAIN RESULTS: Among 979 subjects, 592 (60.5%) had TI using DL with a Macintosh blade, of whom 362 (37%) were intubated with a size 4 blade and 222 (22.7%) with a size 3 blade. We used inverse probability weighting with a propensity score for analyzing data. We found that patients intubated with a size 4 blade had a worse (higher) Cormack-Lehane grade of glottic view than patients intubated with a size 3 blade (adjusted odds ratio [aOR], 1.458; 95% CI, 1.064-2.003; p = 0.02). Patients intubated with a size 4 blade had a lower first pass success than those with a size 3 blade (71.1% vs 81.2%; aOR, 0.566; 95% CI, 0.372-0.850; p = 0.01). CONCLUSIONS AND RELEVANCE: In critically ill adults undergoing TI using DL with a Macintosh blade, patients intubated using a size 4 blade on first attempt had a worse glottic view and a lower first pass success than patients intubated with a size 3 Macintosh blade. Further prospective studies are needed to examine the optimal approach to selecting laryngoscope blade size during TI of critically ill adults.

Time to Renitrogenation After Maximal Denitrogenation in Healthy Volunteers in the Supine and Sitting Positions.

INTRODUCTION: Prior to intubation, preoxygenation is performed to denitrogenate the lungs and create an oxygen reservoir. After oxygen is removed, it is unclear whether renitrogenation after preoxygenation occurs faster in the supine vs the sitting position. METHODS: We enrolled 80 healthy volunteers who underwent two preoxygenation and loss of preoxygenation procedures (one while supine and one while sitting) via bag-valve-mask ventilation with spontaneous breathing. End-tidal oxygen (ETO2) measurements were recorded as fraction of expired oxygen prior to preoxygenation, at the time of adequate preoxygenation (ETO2 >85%), and then every five seconds after the oxygen was removed until the ETO2 values reached their recorded baseline. RESULTS: The mean ETO2 at completion of preoxygenation was 86% (95% confidence interval 85-88%). Volunteers in both the supine and upright position lost >50% of their denitrogenation in less than 60 seconds. Within 25 seconds, all subjects had an ETO2 of <70%. Complete renitrogenation, defined as return to baseline ETO2, occurred in less than 160 seconds for all volunteers. CONCLUSION: Preoxygenation loss, or renitrogenation, occurred rapidly after oxygen removal and was not different in the supine and sitting positions. After maximal denitrogenation in healthy volunteers, renitrogenation occurred rapidly after oxygen removal and was not different in the supine and sitting positions.

Dioxane-Linked Novel Bacterial Topoisomerase Inhibitors Exhibit Bactericidal Activity against Planktonic and Biofilm Staphylococcus aureus In Vitro.

The development of novel treatments for Staphylococcus aureus infections remains a high priority worldwide. We previously reported compounds 0147 and 0186, novel bacterial topoisomerase inhibitors (NBTIs) with potent antibacterial activity against S. aureus, including methicillin-resistant S. aureus. Here, we further investigated the in vitro activity of 0147 and 0186 against S. aureus ATCC 29213. Both compounds demonstrated bactericidal activity against planktonic and biofilm S. aureus, which then translated into significant inhibition of biofilm formation. Combinations of NBTIs and glycopeptides yielded indifferent interactions against planktonic S. aureus, but several had synergistic effects against S. aureus biofilms. This work reinforces the potential of NBTIs as future therapeutics for S. aureus infections. IMPORTANCE The pathogen Staphylococcus aureus contributes substantially to infection-related mortality. Biofilms render bacteria more recalcitrant to antibacterial therapy. The manuscript describes the potent activity of a new class of antibacterial agents against both planktonic and biofilm populations of Staphylococcus aureus.

Limitations of Unipolar Signals in Guiding Successful Outflow Tract Premature Ventricular Contraction Ablation.

BACKGROUND: Unipolar electrograms (UniEGMs) are commonly used to annotate earliest local activation of focal arrhythmias. However, their utility in guiding premature ventricular contractions (PVCs) ablation may be limited when the PVC source is less superficial. OBJECTIVES: The authors sought to compare bipolar electrograms (BiEGMs) vs UniEGMs in guiding successful ablation of right ventricular outflow tract (RVOT) vs intramural outflow tract (OT) PVCs. The authors hypothesized that: 1) earliest bipolar local activation time (LATBi) would better guide mapping and ablation, vs UniEGM dV/dt (LATUni) or QS morphology; and 2) LAT differences using bipolar vs unipolar EGMs (ΔLATBi-Uni) would be greater for intramural OT than RVOT PVCs. METHODS: Consecutive patients undergoing successful PVC ablation 2017 to2020 requiring only RVOT or RVOT+left ventricular OT (RVOT+LVOT) ablation were retrospectively analyzed. BiEGMs and UniEGMs at successful ablation sites were compared. RESULTS: Of 70 patients, 50 required RVOT-only, and 20 required RVOT+LVOT ablation for acute and long-term PVC suppression. Mean ΔLATBi-Uni was lower for RVOT vs RVOT+LVOT groups (9.3 ± 6.4 ms vs 17.4 ± 9.9 ms; P < 0.01). QS UniEGM was seen in 78% of RVOT, compared with 53% of RVOT+LVOT patients (P < 0.016). RVOT+LVOT sites most frequently included the posteroseptal RVOT and adjacent LVOT (73%), and 43% lacked a QS unipolar EGM. ΔLATBi-Uni ≥15 ms best distinguished sites in which RVOT-only vs RVOT+LVOT ablation achieved acute PVC suppression (area under the curve: 0.77). CONCLUSIONS: Earliest BiEGM activation guides successful ablation of OT PVCs better than UniEGM-guided analysis, especially when an intramural PVC source is present.

Aryl Methyl Ketones: Versatile Synthons in the Synthesis of Heterocyclic Compounds.

The synthesis of aromatic heterocycles has attracted substantial attention due to the abundance of these heterocycles in drug molecules, natural products, and other compounds of biological interest. Accordingly, there is a demand for straightforward synthetic protocols toward such compounds using readily available starting materials. In the past decade, there have been substantial developments in heterocycle synthesis, especially in metal-catalyzed and iodine-assisted approaches. This graphical review focuses on notable reactions from the past decade using aryl and heteroaryl methyl ketones as starting materials, including representative reaction mechanisms.

Bag-Mask Ventilation Versus Apneic Oxygenation During Tracheal Intubation in Critically Ill Adults: A Secondary Analysis of 2 Randomized Trials.

Background: Hypoxemia is common during tracheal intubation in intensive care units. To prevent hypoxemia during intubation, 2 methods of delivering oxygen between induction and laryngoscopy have been proposed: bag-mask ventilation and supplemental oxygen delivered by nasal cannula without ventilation (apneic oxygenation). Whether one of these approaches is more effective for preventing hypoxemia during intubation of critically ill patients is unknown. Methods: We performed a secondary analysis of data from 138 patients enrolled in 2, consecutive randomized trials of airway management in an academic intensive care unit. A total of 61 patients were randomized to receive bag-mask ventilation in a trial comparing bag-mask ventilation to none, and 77 patients were randomized to receive 100% oxygen at 15 L/min by nasal cannula in a trial comparing apneic oxygenation to none. Using multivariable linear regression accounting for age, body mass index, severity of illness, and oxygen saturation at induction, we compared patients assigned to bag-mask ventilation with those assigned to apneic oxygenation regarding lowest oxygen saturations from induction to 2 min after intubation. Results: Patients assigned to bag-mask ventilation and apneic oxygenation were similar at baseline. The median lowest oxygen saturation was 96% (interquartile range [IQR] 89%-100%) in the bag-mask ventilation group and 92% (IQR 84%-99%) in the apneic oxygenation group. After adjustment for prespecified confounders, bag-mask ventilation was associated with a higher lowest oxygen saturation compared to apneic oxygenation (mean difference, 4.2%; 95% confidence interval, 0.7%-7.8%; P = .02). The incidence of severe hypoxemia (oxygen saturation<80%) was 6.6% in the bag-mask ventilation group and 15.6% in the apneic oxygenation group (adjusted odds ratio, 0.33; P = .09). Conclusions: This secondary analysis of patients assigned to bag-mask ventilation and apneic oxygenation during 2 clinical trials suggests that bag-mask ventilation is associated with higher oxygen saturation during intubation compared to apneic oxygenation.

Effect of Use of a Bougie vs Endotracheal Tube With Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial.

Importance: For critically ill adults undergoing emergency tracheal intubation, failure to intubate the trachea on the first attempt occurs in up to 20% of cases and is associated with severe hypoxemia and cardiac arrest. Whether using a tracheal tube introducer ("bougie") increases the likelihood of successful intubation compared with using an endotracheal tube with stylet remains uncertain. Objective: To determine the effect of use of a bougie vs an endotracheal tube with stylet on successful intubation on the first attempt. Design, Setting, and Participants: The Bougie or Stylet in Patients Undergoing Intubation Emergently (BOUGIE) trial was a multicenter, randomized clinical trial among 1102 critically ill adults undergoing tracheal intubation in 7 emergency departments and 8 intensive care units in the US between April 29, 2019, and February 14, 2021; the date of final follow-up was March 14, 2021. Interventions: Patients were randomly assigned to use of a bougie (n = 556) or use of an endotracheal tube with stylet (n = 546). Main Outcomes and Measures: The primary outcome was successful intubation on the first attempt. The secondary outcome was the incidence of severe hypoxemia, defined as a peripheral oxygen saturation less than 80%. Results: Among 1106 patients randomized, 1102 (99.6%) completed the trial and were included in the primary analysis (median age, 58 years; 41.0% women). Successful intubation on the first attempt occurred in 447 patients (80.4%) in the bougie group and 453 patients (83.0%) in the stylet group (absolute risk difference, -2.6 percentage points [95% CI, -7.3 to 2.2]; P = .27). A total of 58 patients (11.0%) in the bougie group experienced severe hypoxemia, compared with 46 patients (8.8%) in the stylet group (absolute risk difference, 2.2 percentage points [95% CI, -1.6 to 6.0]). Esophageal intubation occurred in 4 patients (0.7%) in the bougie group and 5 patients (0.9%) in the stylet group, pneumothorax was present after intubation in 14 patients (2.5%) in the bougie group and 15 patients (2.7%) in the stylet group, and injury to oral, glottic, or thoracic structures occurred in 0 patients in the bougie group and 3 patients (0.5%) in the stylet group. Conclusions and Relevance: Among critically ill adults undergoing tracheal intubation, use of a bougie did not significantly increase the incidence of successful intubation on the first attempt compared with use of an endotracheal tube with stylet. Trial Registration: ClinicalTrials.gov Identifier: NCT03928925

Plant functional types broadly describe water use strategies in the Caatinga, a seasonally dry tropical forest in northeast Brazil.

In seasonally dry tropical forests, plant functional type can be classified as deciduous low wood density, deciduous high wood density, or evergreen high wood density species. While deciduousness is often associated with drought-avoidance and low wood density is often associated with tissue water storage, the degree to which these functional types may correspond to diverging and unique water use strategies has not been extensively tested.We examined (a) tolerance to water stress, measured by predawn and mid-day leaf water potential; (b) water use efficiency, measured via foliar δ13C; and (c) access to soil water, measured via stem water δ18O.We found that deciduous low wood density species maintain high leaf water potential and low water use efficiency. Deciduous high wood density species have lower leaf water potential and variable water use efficiency. Both groups rely on shallow soil water. Evergreen high wood density species have low leaf water potential, higher water use efficiency, and access alternative water sources. These findings indicate that deciduous low wood density species are drought avoiders, with a specialized strategy for storing root and stem water. Deciduous high wood density species are moderately drought tolerant, and evergreen high wood density species are the most drought tolerant group.Synthesis. Our results broadly support the plant functional type framework as a way to understand water use strategies, but also highlight species-level differences.

Predictors of first pass success without hypoxemia in trauma patients requiring emergent rapid sequence intubation.

OBJECTIVE: The predictors of first pass success (FPS) without hypoxemia among trauma patients requiring rapid sequence intubation (RSI) in the emergent setting are unknown. METHODS: Retrospective study of adult trauma patients requiring RSI during a 5-year period comparing the trauma patients achieving FPS without hypoxemia to those who did not. The primary outcome was FPS without hypoxemia evaluated by multivariate logistic regression adjusting for the neuromuscular blocking agent used (succinylcholine or rocuronium), hypoxemia prior to RSI, Glasgow Coma Scale (GCS) scores, the presence of head or facial trauma, and intubating operator level of training. RESULTS: 246 patients met our inclusion criteria. The overall FPS rate was 89%, and there was no statistical difference between those receiving either paralytic agent. 167 (69%) patients achieved FPS without hypoxemia. The two groups (those achieving FPS without hypoxemia and those who did not) had similar mean GCS, mean Injury Severity Scores, presence of head or facial trauma, the presence of penetrating trauma, intubating operator-level training, use of direct laryngoscopy, hypoxemia prior to RSI, heart rate per minute, mean systolic blood pressure, and respiratory rate. In the multivariate regression analysis, the use of succinylcholine and GCS score of 13-15 were found to have adjusted ORs of 2.1 (95% CI 1.2 to 3.8) and 2.0 (95% CI 1.0 to 3.3) for FPS without hypoxemia, respectively. CONCLUSION: Trauma patients requiring emergency department RSI with high GCS score and those who received succinylcholine had higher odds of achieving FPS without hypoxemia, a patient safety goal requiring more study. LEVEL OF EVIDENCE: IV. STUDY TYPE: Prognostic.

An umbrella review of effect size, bias, and power across meta-analyses in emergency medicine.

OBJECTIVES: The objective of this study was to conduct an umbrella review of therapeutic studies relevant to emergency medicine, analyzing patterns in effect size, power, and signals of potential bias across an entire field of clinical research. METHODS: We combined topic- and journal-driven searches of PubMed and Google Scholar for published articles of systematic reviews and meta-analyses (SRMA) relevant to emergency medicine (last search in November 2020). Data were screened and extracted by six investigators. Redundant meta-analyses were removed. Whenever possible for each comparison we extracted one meta-analysis on mortality with the most events and one meta-analysis on a nonmortality outcome with the most studies. From each meta-analysis we extracted all individual study effects; outcomes were converted to odds ratios (ORs) and placed on a common scale where an OR < 1.0 represents a reduction in a harmful outcome with an experimental treatment versus control. Outcomes were analyzed at the level of individual studies and at the level of summary effects across meta-analyses. RESULTS: A total of 332 articles contained 431 eligible meta-analyses with a total of 3,129 individual study outcomes; of these, 2,593 (83%) were from randomized controlled trials. The median OR across all studies was 0.70. Within each meta-analysis, the earliest study effect on average demonstrated larger benefit compared to the overall summary effect. Only 57 of 431 meta-analyses (13%) both favored the experimental intervention and did not show any signal of small study effects or excess significance, and of those only 12 had at least one study with 80% or higher power to detect an OR of 0.70. Of these, no interventions significantly decreased mortality in well-powered trials. Although the power of studies increased somewhat over time, the majority of studies were underpowered. CONCLUSIONS: Few interventions studied within SRMAs relevant to emergency medicine seem to have strong and unbiased evidence for improving outcomes. The field would benefit from more optimally powered trials.

Extensive Variation in Drought-Induced Gene Expression Changes Between Loblolly Pine Genotypes.

Drought response is coordinated through expression changes in a large suite of genes. Interspecific variation in this response is common and associated with drought-tolerant and -sensitive genotypes. The extent to which different genetic networks orchestrate the adjustments to water deficit in tolerant and sensitive genotypes has not been fully elucidated, particularly in non-model or woody plants. Differential expression analysis via RNA-seq was evaluated in root tissue exposed to simulated drought conditions in two loblolly pine (Pinus taeda L.) clones with contrasting tolerance to drought. Loblolly pine is the prevalent conifer in southeastern U.S. and a major commercial forestry species worldwide. Significant changes in gene expression levels were found in more than 4,000 transcripts [drought-related transcripts (DRTs)]. Genotype by environment (GxE) interactions were prevalent, suggesting that different cohorts of genes are influenced by drought conditions in the tolerant vs. sensitive genotypes. Functional annotation categories and metabolic pathways associated with DRTs showed higher levels of overlap between clones, with the notable exception of GO categories in upregulated DRTs. Conversely, both differentially expressed transcription factors (TFs) and TF families were largely different between clones. Our results indicate that the response of a drought-tolerant loblolly pine genotype vs. a sensitive genotype to water limitation is remarkably different on a gene-by-gene level, although it involves similar genetic networks. Upregulated transcripts under drought conditions represent the most diverging component between genotypes, which might depend on the activation and repression of substantially different groups of TFs.

Early Intubation and Increased Coronavirus Disease 2019 Mortality: A Propensity Score-Matched Retrospective Cohort Study.

OBJECTIVES: There has been controversy about the timing and indications for intubation and mechanical ventilation in novel coronavirus disease 2019. This study assessed the effect of early intubation and mechanical ventilation on all-cause, inhospital mortality for coronavirus disease 2019 patients. DESIGN: Multicenter retrospective cohort study. SETTING: Eleven municipal hospitals in New York City from March 1, 2020, to December 1, 2020. PATIENTS: Adult patients who tested positive for coronavirus disease 2019 in the emergency department were subsequently admitted. Patients with do-not-intubate orders at admission were excluded. INTERVENTIONS: Intubation within 48 hours of triage and intubation at any point during hospital stay. MEASUREMENTS AND MAIN RESULTS: Data from 7,597 coronavirus disease 2019 patients were included; of these, 1,628 (21%) were intubated overall and 807 (11%) were intubated within 48 hours of triage. After controlling for available confounders, intubation rates for coronavirus disease 2019 patients varied significantly across hospitals and decreased steadily as the pandemic progressed. After nearest neighbor propensity score matching, intubation within 48 hours of triage was associated with higher all-cause mortality (hazard ratio, 1.30 [1.15-1.48]; p < 0.0001), as was intubation at any time point (hazard ratio, 1.62 [1.45-1.80]; p < 0.0001). Among intubated patients, intubation within 48 hours of triage was not significantly associated with differences in mortality (hazard ratio, 1.09 [0.94-1.26]; p = 0.26). These results remained robust to multiple sensitivity analyses. CONCLUSIONS: Intubation within 48 hours of triage, as well as at any time point in the hospital course, was associated with increased mortality in coronavirus disease 2019 patients in this observational study.