Forrest plot.

<p>Forrest plot summarizing the individual studies and pooled results of the meta-analysis. The relationship between prehospital intubation (PHI) and mortality is stratified by experience of prehospital healthcare providers.</p

Study characteristics.

<p>^a In- and exclusion criteria for the population of interest.</p><p>^b Number of population on which the analyses of interest (prehospital intubation versus no intubation in TBI patients) are based. If multiple analyses are presented in the manuscript, the range of the number of patients used in the analyses is reported.</p><p>^c Data from the studies by Bukur and Karamanos report patients from the same region and overlapping time period.</p><p>^d Data from the studies by Davis, Poste, Sloane and Winchell are all from the same region and overlapping time periods and partially report overlapping data.</p><p>^e Total number of patients in study, unclear whether all are included in analysis of interest.</p><p>^f Data are from the National Trauma Data Bank and might include some patients that have also been included to other studies that have been performed in the USA.</p><p>ABG: arterial blood gas</p><p>(H-)AIS: (head) abbreviated injury scale</p><p>CPR: cardiopulmonary resuscitation</p><p>CT: computed tomography</p><p>ED: emergency department</p><p>GCS: Glasgow Coma Scale</p><p>ICU: intensive care unit</p><p>ICD-9-CM: international classification of diseases, 9^th revision, clinical modification</p><p>ISS: injury severity scale</p><p>NR: not reported</p><p>OR: operating room</p><p>RCT: randomized controlled trial</p><p>RSI: rapid sequence induction</p><p>TBI: traumatic brain injury</p><p>Study characteristics.</p

Mortality.

<p>^a Time of mortality assessment is not explicitly mentioned. However, we strongly assume that it is hospital mortality because no follow-up beyond hospital discharge is reported. For the studies by Davis and colleagues, this assumption is further underlined by the fact that other studies that have been performed by the same study group in the same patient population also regularly report hospital mortality. Requests to the authors to clarify this issue have remained unanswered.</p><p>^b Personal communication by the first author.</p><p>^c Calculated from reported percentages. May not necessarily be exactly the actual number due to rounding or unreported omission of patients from the analysis.</p><p>^d Calculation of the adjusted odds ratio may not necessarily be based on the same number of patients used for calculation of the unadjusted OR (e.g., due to missing covariates in some patients).</p><p>(H-)AIS: (head) abbreviated injury scale</p><p>CI: confidence interval</p><p>ED: emergency department</p><p>EMS: emergency medical services</p><p>GCS: Glasgow Coma Scale</p><p>ICU: intensive care unit</p><p>ISS: injury severity scale</p><p>NA: not applicable</p><p>NR: not reported</p><p>OR: odds ratio</p><p>SBP: systolic blood pressure</p><p>TBI: traumatic brain injury</p><p>Mortality.</p

Quality Assessment.

<p>^a Not selected because of potential overlap with Karamanos (2014).</p><p>^b Several analyses described in the manuscript were eligible; the one with the smallest standard error of the estimated OR was selected.</p><p>^c Study eligible based on quality criteria, but EMS-provider experience was “indeterminate” (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141034#pone.0141034.t003" target="_blank">Table 3</a>).</p><p>^d Several analysis presented; first hour survival and first day survival data are adjusted, however the analysis with the outcome of main interest (hospital mortality) is not adjusted.</p><p>^e Several analyses are presented, among which one matched and one adjusted analyses. Both of these analyses earned two stars for comparability, while the cohorts are not comparable in the crude analyses.</p><p>Newcastle-Ottawa Quality Assessment Scale</p><p>Selection:     1. Representativeness of the exposed cohort (prehospital intubation)</p><p>        2. Selection of the non-exposed cohort (no prehospital intubation)</p><p>        3. Ascertainment of exposure</p><p>    4. Demonstration that outcome of interest was not present at start of study</p><p>Comparability:     5. Comparability of cohorts on the basis of the design or analysis: most important factor</p><p>        6. Comparability of cohorts on the basis of the design or analysis: additional factors</p><p>Outcome:     7. Assessment of outcome</p><p>        8. Was follow-up long enough for outcomes to occur?</p><p>        9. Adequacy of follow up of cohorts</p><p>Cochrane Collaboration’s tool for assessing risk of bias: Domains</p><p>    A. Sequence generation</p><p>    B. Allocation concealment</p><p>    C. Blinding of participants and personnel</p><p>    D. Blinding of outcome assessors</p><p>    E. Incomplete outcome data</p><p>    F. Selective outcome reporting</p><p>    G. Other sources of bias</p><p>Quality Assessment.</p

Treatments.

<p>BPM: beats per minute</p><p>ED: emergency department</p><p>NMBA: neuromuscular blocking agents</p><p>NR: not reported</p><p>RSI: rapid sequence induction</p><p>SBP: systolic blood pressure</p><p>Treatments.</p

Patient and injury characteristics^a.

<p>^a For studies presenting data from several patient populations or several sub-analyses, the reported patient characteristics refer to the total patient population.</p><p>^b Presented as mean, mean ± SD, mean (95% CI), median, median (IQR) or as percentage per category, as reported by the authors or as calculated from the available data.</p><p>^c Multiple analyses with two different control groups (no prehospital invasive airway management, intubation in the emergency department) performed in the study. The presented data are for the subpopulation of patients intubated in the emergency department.</p><p>^d Study reports sub-analyses for patients with isolated TBI.</p><p>GCS: Glasgow Coma Scale; H-AIS: head abbreviated injury scale; ISS: injury severity scale; NR: not reported; TBI: traumatic brain injury</p><p>Patient and injury characteristics<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141034#t003fn001" target="_blank">^a</a>.</p

Enriched Air Nitrox Breathing Reduces Venous Gas Bubbles after Simulated SCUBA Diving: A Double-Blind Cross-Over Randomized Trial

<div><p>Objective</p><p>To test the hypothesis whether enriched air nitrox (EAN) breathing during simulated diving reduces decompression stress when compared to compressed air breathing as assessed by intravascular bubble formation after decompression.</p><p>Methods</p><p>Human volunteers underwent a first simulated dive breathing compressed air to include subjects prone to post-decompression venous gas bubbling. Twelve subjects prone to bubbling underwent a double-blind, randomized, cross-over trial including one simulated dive breathing compressed air, and one dive breathing EAN (36% O₂) in a hyperbaric chamber, with identical diving profiles (28 msw for 55 minutes). Intravascular bubble formation was assessed after decompression using pulmonary artery pulsed Doppler.</p><p>Results</p><p>Twelve subjects showing high bubble production were included for the cross-over trial, and all completed the experimental protocol. In the randomized protocol, EAN significantly reduced the bubble score at all time points (cumulative bubble scores: 1 [0–3.5] vs. 8 [4.5–10]; P < 0.001). Three decompression incidents, all presenting as cutaneous itching, occurred in the air versus zero in the EAN group (P = 0.217). Weak correlations were observed between bubble scores and age or body mass index, respectively.</p><p>Conclusion</p><p>EAN breathing markedly reduces venous gas bubble emboli after decompression in volunteers selected for susceptibility for intravascular bubble formation. When using similar diving profiles and avoiding oxygen toxicity limits, EAN increases safety of diving as compared to compressed air breathing.</p><p>Trial Registration</p><p><a href="http://www.isrctn.com/ISRCTN31681480" target="_blank">ISRCTN 31681480</a></p></div

Inclusion and randomization flow diagram.

<p>EAN = Enriched air nitrox.</p

Intravascular bubble score.

<p>Intravascular bubble score.</p

Intravascular bubble scores of two air dives.

<p>Intravascular bubble scores of two air dives.</p