Search

Introduction Guidelines recommend the use of direct oral anticoagulation therapy over warfarin for the treatment of venous thromboembolism and atrial fibrillation. However, there is uncertainty and a lack of data supporting the safety and efficacy of anticoagulation therapy in lung transplant recipients. Additionally, there are unique considerations for this population, such as labile renal function and drug interactions. Project Aims The objective of this program evaluation was to evaluate the safety and efficacy of apixaban therapy for atrial fibrillation and venous thromboembolism in lung transplant recipients. Design Medical records of all adult lung transplant recipients who received apixaban for atrial fibrillation or venous thromboembolism treatment between January 1, 2018, and August 31, 2020 were retrospectively reviewed. Safety was evaluated by the incidence of bleeding. Efficacy was evaluated by the recurrence of blood clots or the incidence of stroke. Results A total of 134 recipients were included in the review. Thromboembolisms occurred in 14 recipients (10%), and none experienced a stroke. Bleeding occurred in 12 recipients (9%). Conclusions The results of this evaluation were similar to those seen in smaller studies of the safety and efficacy of direct oral anticoagulation therapy for the treatment of atrial fibrillation or venous thromboembolism in lung transplant recipients, especially in recipients taking interacting azole antifungals. Prospective, comparative studies are needed to confirm these findings.

The natural advantages of sulfur in adhesion and dynamic exchanges are combined with epoxies to achieve high-strength debondable adhesives.

Little is known about the out-of-hospital blood pressure ranges associated with optimal outcomes in traumatic brain injuries (TBI). Our objective was to evaluate the associations between out-of-hospital systolic blood pressure (SBP) and multiple hospital outcomes without assuming any predefined thresholds for hypotension, normotension, or hypertension.This was a preplanned secondary analysis from the Excellence in Prehospital Injury Care (EPIC) TBI study. Among patients (age ≥10 years) with major TBIs (Barell Matrix type 1 and/or Abbreviated Injury Scale-head severity ≥3) and lowest out-of-hospital SBPs of 40 to 299 mmHg, we utilized generalized additive models to summarize the distributions of various outcomes as smoothed functions of SBP, adjusting for important and significant confounders. The subjects who were enrolled in the study phase after the out-of-hospital TBI guideline implementation were used to validate the models developed from the preimplementation cohort.Among 12,169 included cases, the mortality model revealed 3 distinct ranges: (1) a monotonically decreasing relationship between SBP and the adjusted probability of death from 40 to 130 mmHg, (2) lowest adjusted mortality from 130 to 180 mmHg, and (3) rapidly increasing mortality above 180 mmHg. A subanalysis of the cohorts with isolated TBIs and multisystem injuries with TBIs revealed SBP mortality patterns that were similar to each other and to that of the main analysis. While the specific SBP ranges varied somewhat for the nonmortality outcomes (hospital length of stay, ICU length of stay, discharge to skilled nursing/inpatient rehabilitation, and hospital charges), the patterns were very similar to that of mortality. In each model, validation was confirmed utilizing the postimplementation cohort.Optimal adjusted mortality was associated with a surprisingly high SBP range (130 to 180 mmHg). Below this level, there was no point or range of inflection that would indicate a physiologically meaningful threshold for defining hypotension. Nonmortality outcomes showed very similar patterns. These findings highlight how sensitive the injured brain is to compromised perfusion at SBP levels that, heretofore, have been considered adequate or even normal. While the study design does did not allow us to conclude that the currently recommended treatment threshold (90 mmHg) should be increased, the findings imply that the definition of hypotension in the setting of TBI is too low. Randomized trials evaluating treatment levels significantly higher than 90 mmHg are needed.

Supplementary Figure Legends from Activation of the PI3K/Akt/mTOR and MAPK Signaling Pathways in Response to Acute Solar-Simulated Light Exposure of Human Skin

The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced nonmelanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared with those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here, we explored the use of topical rapamycin as a chemopreventive agent in the context of solar-simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared with controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared with vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC. Cancer Prev Res; 9(3); 215–24. ©2016 AACR.

Supplementary Figure 1. Box plot graphs of protein expression in sun-protected skin after 2, 2,5, and 3 MED (x-axis) of SSL-irradiation (SSL) with baseline (green bars), 5 minutes (orange bars), 1 hour (blue bars), 5 hours (red bars), and 24 hours (grey bars) post SSL on the y-axis. Supplementary Figure 2. Box plot graphs of protein expression in sun-protected skin after 2, 2,5, and 3 MED (x-axis) of SSL-irradiation (SSL) with baseline (green bars), 5 minutes (orange bars), 1 hour (blue bars), 5 hours (red bars), and 24 hours (grey bars) post SSL on the y-axis. Supplementary Figure 3. Box plot graphs of protein expression in sun-protected skin after 2, 2,5, and 3 MED (x-axis) of SSL-irradiation (SSL) with baseline (green bars), 5 minutes (orange bars), 1 hour (blue bars), 5 hours (red bars), and 24 hours (grey bars) post SSL on the y-axis.

Schema representing UV-induced signaling, rapamycin and PHT-427-regulated pathways in keratinocytes.

The incidence of skin cancer is higher than all other cancers and continues to increase, with an average annual cost over $8 billion in the United States. As a result, identifying molecular pathway alterations that occur with UV exposure to strategize more effective preventive and therapeutic approaches is essential. To that end, we evaluated phosphorylation of proteins within the PI3K/Akt and MAPK pathways by immunohistochemistry in sun-protected skin after acute doses of physiologically relevant solar-simulated ultraviolet light (SSL) in 24 volunteers. Biopsies were performed at baseline, 5 minutes, 1, 5, and 24 hours after SSL irradiation. Within the PI3K/Akt pathway, we found activation of Akt (serine 473) to be significantly increased at 5 hours while mTOR (serine 2448) was strongly activated early and was sustained over 24 hours after SSL. Downstream, we observed a marked and sustained increase in phospho-S6 (serine 235/S236), whereas phospho-4E-BP1 (threonines 37/46) was increased only at 24 hours. Within the MAPK pathway, SSL-induced expression of phospho-p38 (threonine 180/tyrosine 182) peaked at 1 to 5 hours. ERK 1/2 was observed to be immediate and sustained after SSL irradiation. Phosphorylation of histone H3 (serine 10), a core structural protein of the nucleosome, peaked at 5 hours after SSL irradiation. The expression of both p53 and COX-2 was increased at 5 hours and was maximal at 24 hours after SSL irradiation. Apoptosis was significantly increased at 24 hours as expected and indicative of a sunburn-type response to SSL. Understanding the timing of key protein expression changes in response to SSL will aid in development of mechanistic-based approaches for the prevention and control of skin cancers. Cancer Prev Res; 8(8); 720–8. ©2015 AACR.

Supplementary Figure Legends - PDF file 90K, Figure legends for Supplementary Material

Figure S2 - PDF file 2023K, IHC images for HIF-1� and SHH in patient matched tumor TMA cores

Figures S3 to S7 and Tables S1 and S2 - PDF file 532K, S3 Kaplan-Meier patient survival analyses reveals no correlation between survival and PTCH levels. S4 Survival plots based on the univariate table S5 Increased expression of SHH during hypoxia in pancreatic cancer cell lines. S6 A HIF1-�- and SHH-dependent activation of hedgehog signaling in fibroblasts grown in 3D co-cultures with Panc-1 cells. S7, SHH formation by pancreatic cancer cells in hypoxia is mediating the desmoplastic reaction in fibroblasts Table S1 Univariate table showing that high histologic grade Table S2 A pathway array profiling the expression of genes involved in hedgehog signaling in MiaPaca 2 cells transfected with shHIF-1� in normoxia and hypoxia

IntroductionThe Arizona Surge Line was an emergent initiative during the COVID-19 pandemic to facilitate COVID-19 patient transfers and load-level hospitals on a statewide level. It was designed and implemented by the Arizona Department of Health Services in preparation for the first hospital surge due to COVID-19, recognizing the disproportionate impact that hospital surge would have on rural and tribal populations.MethodsWe analyzed the Arizona Surge Line transfer data for the state's first two COVID-19 surges (4/16/2020–3/6/2021). Transfer data included transfer request characteristics, patient demographics and participating hospital characteristics. When applicable, we compared this data with Arizona census data, COVID-19 case data, and the CDC/ATSDR Social Vulnerability Index. The primary outcomes studied were the proportion of COVID-19 patient requests being successfully transferred, the median transfer time, and the proportion of vulnerable populations impacted.ResultsDuring the period of study, 160 hospitals in Arizona made 6,732 requests for transfer of COVID-19 patients. The majority of these patients (84%, 95% CI: 83–85%) were placed successfully with a median transfer time of 59 min (inter-quartile range 33–116). Of all transfer requests, 58% originated from rural hospitals, 53% were for patients of American Indian/Alaska Native ethnicity, and 73% of patients originated from highly vulnerable areas. The majority (98%) of receiving facilities were in urban areas. The Arizona Surge Line matched the number of transfers with licensed market shares during the period of study.ConclusionsThe Arizona Surge Line is an equity-enhancing initiative that disproportionately benefited vulnerable populations. This statewide transfer infrastructure could become a standard public health mechanism to manage hospital surges and enhance access to care during a health emergency.

Serotonin 2A receptors (5-HT

Bioaugmentation is considered as an attractive method for nitrogen removal in water treatment, but its effectiveness in actual high-strength piggery wastewater has not been adequately verified and the mechanism of bioaugmentation in actual wastewater treatment system is not very clear especially from the perspectives of microbial communities and functional genes. This study investigated the mechanisms of a heterotrophic nitrifying-aerobic denitrifying strain Alcaligenes aquatilis AS1 in the bioaugmentation of continuous biological nitrogen removal of actual piggery wastewater at laboratory scale. The addition of strain AS1 significantly improved the nitrogen removal efficiency (more than 95% of NH

Minimally invasive hysterectomy is a commonly performed gynecologic procedure with associated postoperative pain managed with opioid medications. Uncontrolled postoperative pain leads to increased opioid use/abuse, longer hospital stays, increase in healthcare visits, and may negatively affect patient satisfaction. Current data suggests that reduced pneumoperitoneum insufflation pressure during laparoscopic surgery may impact postoperative pain. Given the current opioid epidemic, surgeons are proactively finding ways to reduce postoperative pain. It is unclear how reduced pneumoperitoneum pressure impacts the surgeon. We investigated the impact of reduced pneumoperitoneum insufflation pressure on surgeon satisfaction.This was a pilot, double-blinded, randomized controlled trial from March 2020 to July 2021 comparing pneumoperitoneum pressure of 15 mmHg to reduced pressures of 12 mmHg and 10 mmHg during laparoscopic hysterectomy.A total of 40 patients were randomized (13 - 15 mmHg, 13 - 12 mmHg, and 14 - 10 mmHg). The primary outcome was surgeon satisfaction. Secondary outcomes included patient satisfaction, operative time, blood loss, postoperative pain, opioid usage, and discharge timing. There were no differences in baseline demographics or perioperative characteristics. Surgeon satisfaction was negatively impacted with lower pneumoperitoneum pressures greatest with 10 mmHg, including overall satisfaction (p =.01), overall effect of the pneumoperitoneum (p =.04), and quality of visualization (p =.01). There was an apparent although not statistically significant difference in operative time (p =.06) and blood loss (p =.054). There was no difference in patient satisfaction, postoperative pain scores, opioid usage, or time to discharge.Reduced pneumoperitoneum insufflation pressure during laparoscopic hysterectomy negatively impacted surgeon satisfaction with a trend towards longer operative times and greater blood loss, and did not positively impact patient satisfaction, postoperative pain, opioid demand, or discharge timing.

Hypotension has a powerful effect on patient outcome after traumatic brain injury (TBI). The relative impact of hypotension occurring in the field versus during early hospital resuscitation is unknown. We evaluated the association between hypotension and mortality and non-mortality outcomes in four cohorts defined by where the hypotension occurred [neither prehospital nor hospital, prehospital only, hospital only, both prehospital and hospital].Subjects ≥10 years with major TBI were included. Standard statistics were used for unadjusted analyses. We used logistic regression, controlling for significant confounders, to determine the adjusted odds (aOR) for outcomes in each of the three cohorts.Included were 12,582 subjects (69.8% male; median age 44 (IQR 26-61). Mortality by hypotension status: No hypotension: 9.2% (95%CI: 8.7-9.8%); EMS hypotension only: 27.8% (24.6-31.2%); hospital hypotension only: 45.6% (39.1-52.1%); combined EMS/hospital hypotension 57.6% (50.0-65.0%); (p0.0001). The aOR for death reflected the same progression: 1.0 (reference-no hypotension), 1.8 (1.39-2.33), 2.61 (1.73-3.94), and 4.36 (2.78-6.84), respectively. The proportion of subjects having hospital hypotension was 19.0% (16.5-21.7%) in those with EMS hypotension compared to 2.0% (1.8-2.3%) for those without (p0.0001). Additionally, the proportion of patients with TC hypotension was increased even with EMS "near hypotension" up to an SBP of 120 mmHg [(aOR 3.78 (2.97, 4.82)].While patients with hypotension in the field or on arrival at the trauma center had markedly increased risk of death compared to those with no hypotension, those with prehospital hypotension that was not resolved before hospital arrival had, by far, the highest odds of death. Furthermore, TBI patients who had prehospital hypotension were five times more likely to arrive hypotensive at the trauma center than those who did not. Finally, even "near-hypotension" in the field was strongly and independently associated the risk of a hypotensive hospital arrival (90 mmHg). These findings are supportive of the prehospital guidelines that recommend aggressive prevention and treatment of hypotension in major TBI.

BackgroundThe biological consequences of stress from the social environment pattern health outcomes. This study investigated whether social stress is prospectively associated with fracture incidence among racially and ethnically diverse, postmenopausal women.MethodsData from 160 709 postmenopausal women in the Women’s Health Initiative was analysed using Cox proportional hazards regression models to examine prospective associations of social stress with time to total and hip fracture incidence. Self-reported questionnaires measuring social strain, social functioning and social support were used to assess social stress.ResultsAge and race/ethnicity modified associations between social stress and total and hip fractures. HRs for the associations between higher social support (indicating lower social stress) and total fractures among those age 50–59 years were 0.92 (95% CI: 0.90 to 0.94); HR=0.94 (95% CI: 0.93 to 0.95) for those age 60–69 years and HR=0.96 (95% CI: 0.95 to 0.98) for those age 70–79 years. Higher social strain was associated with greater hip fracture incidence among Native American women (HR=1.84, 95% CI: 1.10 to 3.10), Asian women (HR=1.37, 95% CI: 1.01 to 1.86) and white women (HR=1.04, 95% CI: 1.01 to 1.08).ConclusionIdentifying population patterns of fracture incidence as biological expressions of social environments reveals how race/ethnic specific social environmental factors influence disparities in fractures.

To identify the relationship between patient position during surgery and time to confirmation of ureteral patency on cystoscopy.Randomized controlled trial.Academic tertiary care medical center.A total of 91 adult women undergoing laparoscopic (either conventional or robotic) hysterectomy between February 2021 and February 2022 were randomized to intervention (n = 45) or control (n = 46). Exclusion criteria included known kidney disease or urinary tract anomaly, current ureteral stent, pregnancy, malignancy, and recognized intraoperative urinary tract injury.Subjects in the control group were placed in a 0° supine position during cystoscopy. Subjects in the intervention group were placed in a 20° angle in reverse Trendelenburg (RT) position during cystoscopy.The primary outcome, time to confirmation of bilateral ureteral patency, was measured at the time the second ureteral jet was viewed during intraoperative cystoscopy. There was no significant difference in mean time to confirmation (66.5 seconds in supine vs 67 seconds in RT, p = .2) nor in total cystoscopy time (111 seconds in supine vs 104.5 seconds in RT, p = .39). There were no significant differences in need for alternative modalities to aid in ureteral efflux visualization, delayed diagnosis of ureteric injury, and operative time. RT position seemed to have reduced the time to confirmation for the small group of patients with longer confirmation time (120 seconds).RT position does not change time to confirmation of bilateral ureteral patency compared with supine position. However, there may be a benefit in position change if time to confirmation is120 seconds.

The emergence of antifungal resistance, especially to the most widely used azole class of ergosterol biosynthesis inhibitors, makes fungal infections difficult to treat in clinics and agriculture. When exposed to azoles, fungi can make adaptive responses to alleviate azole toxicity and produce azole tolerance. However, except for azole efflux pumps and ergosterol biosynthesis genes, the role of most azole responsive genes in azole resistance is unknown. In this study, STK-17, whose transcription is upregulated by azoles, was characterized as a novel kinase that is required for azole resistance. Deletion or dysfunction of STK-17 led to azole hypersensitivity in Neurospora crassa and to other ergosterol biosynthesis inhibitors such as amorolfine, terbinafine, and amphotericin B, but not fatty acid and ceramide biosynthesis inhibitors. STK-17 was also required for oxidative stress resistance, but this was not connected to azole resistance. RNA-seq results showed that

Multidrug resistance, defined as the resistance to multiple drugs in different categories, has been an increasing serious problem. Limited antifungal drugs and the rapid emergence of antifungal resistance prompt a thorough understanding of how the occurrence of multidrug resistance develops and which mechanisms are involved. In this study, experimental evolution was performed under single-azole-drug stress with the model filamentous fungus

Missingness mechanism is in theory unverifiable based only on observed data. If there is a suspicion of missing not at random, researchers often perform a sensitivity analysis to evaluate the impact of various missingness mechanisms. In general, sensitivity analysis approaches require a full specification of the relationship between missing values and missingness probabilities. Such relationship can be specified based on a selection model, a pattern-mixture model or a shared parameter model. Under the selection modeling framework, we propose a sensitivity analysis approach using a nonparametric multiple imputation strategy. The proposed approach only requires specifying the correlation coefficient between missing values and selection (response) probabilities under a selection model. The correlation coefficient is a standardized measure and can be used as a natural sensitivity analysis parameter. The sensitivity analysis involves multiple imputations of missing values, yet the sensitivity parameter is only used to select imputing/donor sets. Hence, the proposed approach might be more robust against misspecifications of the sensitivity parameter. For illustration, the proposed approach is applied to incomplete measurements of level of preoperative Hemoglobin A1c, for patients who had high-grade carotid artery stenosisa and were scheduled for surgery. A simulation study is conducted to evaluate the performance of the proposed approach.

Introduction Emergency service vehicle crashes (ESVCs), including rollovers and collisions with other vehicles and fixed objects, are a leading cause of death among U.S. firefighters. Risk management (RM) is a proactive intervention to identifying and mitigating occupational risks and hazards. The goal of this study was to assess the effect of RM in reducing ESVCs. Methods: Three fire departments (A, B and C), representing urban and suburban geographies, and serving medium to large populations, participated in facilitated RM programs to reduce their ESVCs. Interventions were chosen by each department to address their department-specific circumstances and highest risks. Monthly crash rates per 10,000 calls were calculated for each department an average of 28 months before and 23 months after the start of the RM programs. Interrupted time series analysis was used to assess the effect of the RM programs on monthly crash rates. Poisson regression was used to estimate the number of crashes avoided. Economic data from Department A were analyzed to estimate cost savings. Results: Department A had a 15.4% (P = 0.30) reduction in the overall monthly crash rate immediately post-RM and a 1% (P = 0.18) decline per month thereafter. The estimated two-year average cost savings due to 167 crashes avoided was $253,100 (95%CI= $192,355 – $313,885). Department B had a 9.7% (P = 0.70) increase in the overall monthly crash rate immediately post-RM and showed no significant changes in their monthly crash rate. Department C had a 28.4% (P = 0.001) reduction in overall monthly crash rate immediately post-RM and a 1.2% (P = 0.09) increase per month thereafter, with an estimated 122 crashes avoided. Conclusions: RM programs have the potential to reduce ESVCs in the fire service and their associated costs; results may vary based on the interventions chosen and how they are implemented. Practical applications: Risk management may be an effective and broadly implemented intervention to reduce ESVCs in the US fire service.

Higher chest compression release velocity (CCRV) has been associated with better outcomes after out-of-hospital cardiac arrest (OHCA), and patient factors have been associated with variations in chest wall compliance and compressibility. We evaluated whether patient sex, age, weight, and time in resuscitation were associated with CCRV during pre-hospital resuscitation from OHCA.Observational study of prospectively collected OHCA quality improvement data in two suburban EMS agencies in Arizona between 10/1/2008 and 12/31/2016. Subject-level mean CCRV during the first 10 min of compressions was correlated with categorical variables by the Wilcoxon rank-sum test and with continuous variables by the Spearman's rank correlation coefficient. Generalized estimating equation and linear mixed-effect models were used to study the trend of CCRV over time.During the study period, 2535 adult OHCA cases were treated. After exclusion criteria, 1140 cases remained for analysis. Median duration of recorded compressions was 8.70 min during the first 10 min of CPR. An overall decline in CCRV was observed even after adjusting for compression depth. The subject-level mean CCRV was higher for minutes 0-5 than for minutes 5-10 (mean 347.9 mm/s vs. 339.0 mm/s, 95% CI of the difference -12.4 to -5.4, p 0.0001). Males exhibited a greater mean CCRV compared to females [344.4 mm/s (IQR 307.3-384.6) vs. 331.5 mm/s (IQR 285.3-385.5), p = 0.013]. Mean CCRV was negatively correlated with age and positively correlated with patient weight.CCRV declines significantly over the course of resuscitation. Patient characteristics including male sex, younger age, and increased weight were associated with a higher CCRV.

Background: Studies show that EMS patients are often inadvertently hyperventilated (HV), resulting in hypocapnia. In TBI, HV markedly increases mortality. We evaluated continuous prehospital ETCO2 data in intubated TBI patients. Methods: Analysis of monitor data files (Philips MRx™) from a sample of intubated TBI cases in the EPIC Study (NIH-R01NS071049). Results: Among hundreds of cases, graphical display of continuous ETCO2 from 3 subjects dramatically exemplified commonly-occurring inadvertent HV. Fig 1 shows unrecognized HV lasting nearly 15 min. Fig 2 reveals nearly 14 min of increasing ventilatory rate and progressively worsening hypocapnia. Fig 3 shows nearly 4 min of HV that ends abruptly with clear, sudden recognition and slowing of ventilatory rate that leads to restoration of normal ETCO2 in only a few breaths. The corresponding EMS patient care records (PCR) failed to document the presence, severity, and duration of HV. Conclusions: In a study emphasizing prevention of HV, subsequent evaluation of continuous ETCO2 data revealed many cases of unintentionally rapid manual ventilation and severe hypocapnia, often occurring for long periods. These findings, even in the face of explicit guideline-based training, demonstrate a clear need for routine access to continuous monitor data among intubated patients for quality improvement and in clinical studies. Review of PCRs does not reliably identify mismanagement of ventilation. Furthermore, these findings make it likely that real-time audiovisual feedback technology would improve ventilatory management by alerting providers to unidentified HV that results from the frequent distractions occurring during EMS care.

Background: Little is known about the provision of care by law enforcement (LE) personnel within modern EMS systems. We evaluated LE performance of bystander CPR (BCPR) and associated outcomes in OHCA across Arizona. Methods: A total of 5,654 OHCA cases (1/1/2019-12/31/2019) were evaluated using the Save Hearts in Arizona Registry and Education (SHARE) cardiac arrest registry. Data were abstracted from all EMS patient care records (PCRs). If two parties provided BCPR, the first to give compressions was considered the provider for this analysis. Cases identified as “Stranger” or “Unknown” BCPR were manually evaluated for narrative data to identify BCPR provider when possible. Results: BCPR was provided in 2285 cases [48.8%; (95% CIs 47.4%, 50.3%)] after excluding 850 cases that occurred in healthcare facilities where personnel are duty-bound to provide CPR. LE provided BCPR in 444 patients [19.4% (17.8%, 21.1%)], second only to family/spouse [1143 pts; 50.0% (48.0%, 52.1%)]. Overall, 279 patients survived to hospital discharge [12.2%, (10.9%, 13.6%)]. The Table shows the rates of BCPR in each provider category and the associated rates of survival. Of note is that the rate of bystander AED use was more than four times higher in LE BCPR [6.3% (4.23%, 8.99%)] than family-provided BCPR [1.5% (0.87%, 2.37%; p < 0.0001)], but was still very low. Conclusions: In this statewide study that included more than 130 EMS agencies from frontier to urban settings, LE personnel were frequently involved in the care of OHCA patients within the 911 system response. To our knowledge, this magnitude of provision of BCPR by LE (nearly one in five BCPR cases) has not been reported previously. Furthermore, the consequential rate of LE response to OHCA provides the opportunity to significantly increase AED use. Our findings support the widespread and intentional training of LE in CPR and AED use and has the potential to improve survival in diverse settings.

Cotton is the most important fiber crop and provides indispensable natural fibers for the textile industry. Micronaire (MIC) is determined by fiber fineness and maturity and is an important component of fiber quality. Gossypium barbadense L. possesses long, strong and fine fibers, while upland cotton (Gossypium hirsutum L.) is high yielding with high MIC and widely cultivated worldwide. To identify quantitative trait loci (QTLs) and candidate genes for MIC in G. barbadense, a population of 250 backcross inbred lines (BILs), developed from an interspecific cross of upland cotton CRI36 × Egyptian cotton (G. barbadense) Hai7124, was evaluated in 9 replicated field tests. Based on a high-density genetic map with 7709 genotyping-by-sequencing (GBS)-based single-nucleotide polymorphism (SNP) markers, 25 MIC QTLs were identified, including 12 previously described QTLs and 13 new QTLs. Importantly, two stable MIC QTLs (qMIC-D03-2 on D03 and qMIC-D08-1 on D08) were identified. Of a total of 338 genes identified within the two QTL regions, eight candidate genes with differential expression between TM-1 and Hai7124 were identified. Our research provides valuable information for improving MIC in cotton breeding.

De novo donor-specific antibodies (DSAs) increase the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Both carfilzomib (CFZ) and rituximab (RTX) lower the mean fluorescent intensity (MFI) of DSAs, but comparative data are lacking. We compared CLAD-free survival and the degree and duration of DSA depletion after treatment of LTRs with CFZ or RTX.LTRs that received CFZ or RTX for DSA depletion between 08/01/2015 and 08/31/2020 were included. The primary outcome was CLAD-free survival. Secondary outcomes were change in MFI at corresponding loci within 6 months of treatment (ΔMFI), time to DSA rebound, and change in % predicted FEVForty-four LTRs were identified, 7 of whom had ≥2 drug events; therefore, 53 drug events were divided into 2 groups, CFZ (n = 17) and RTX (n = 36). Use of plasmapheresis, immunoglobulin, and mycophenolate augmentation was equivalent in both groups. CLAD-free survival with a single RTX event was superior to that after ≥2 drug events (p = 0.001) but comparable to that with a single CFZ event (p = 0.399). Both drugs significantly lowered the MFI at DQ locus, and the median ΔMFI was comparable. Compared to the RTX group, the CFZ group had a shorter median interval to DSA rebound (p = 0.015) and a lower ΔFEVAlthough both CFZ and RTX reduced the MFI of circulating DSAs, RTX prolonged the time to DSA rebound. Despite more pronounced improvement in FEV

Simple Summary The assessment of actinic keratoses (AKs) in prevention and therapeutic trials, as well as clinical practice, could significantly benefit from the incorporation of non-invasive imaging technology. Such technology has the potential to enhance the objective evaluation of clinical and subclinical AKs with the added advantage of sequential monitoring. In vivo reflectance confocal microscopy (RCM) allows for the non-invasive imaging of AKs at a cellular level. We aimed to establish an in in vivo RCM protocol for AK response monitoring, ultimately leading to more reliable characterization of longitudinal responses and therapy optimization. Abstract Reflectance confocal microscopy (RCM) presents a non-invasive method to image actinic keratosis (AK) at a cellular level. However, RCM criteria for AK response monitoring vary across studies and a universal, standardized approach is lacking. We aimed to identify reliable AK response criteria and to compare the clinical and RCM evaluation of responses across AK severity grades. Twenty patients were included and randomized to receive either cryotherapy (n = 10) or PDT (n = 10). Clinical assessment and RCM evaluation of 12 criteria were performed in AK lesions and photodamaged skin at baseline, 3 and 6 months. We identified the RCM criteria that reliably characterize AK at baseline and display significant reduction following treatment. Those with the highest baseline odds ratio (OR), good interobserver agreement, and most significant change over time were atypical honeycomb pattern (OR: 12.7, CI: 5.7–28.1), hyperkeratosis (OR: 13.6, CI: 5.3–34.9), stratum corneum disruption (OR: 7.8, CI: 3.5–17.3), and disarranged epidermal pattern (OR: 6.5, CI: 2.9–14.8). Clinical evaluation demonstrated a significant treatment response without relapse. However, in grade 2 AK, 10/12 RCM parameters increased from 3 to 6 months, which suggested early subclinical recurrence detection by RCM. Incorporating standardized RCM protocols for the assessment of AK may enable a more meaningful comparison across clinical trials, while allowing for the early detection of relapses and evaluation of biological responses to therapy over time.

Few studies have focused on intraoperative positioning as a risk factor for venous thromboembolism (VTE). Positioning that places the legs in a dependent position may be a risk factor. We theorized that the reverse-Trendelenburg position specifically would increase the risk of postoperative VTE.374,017 subjects undergoing laparoscopic surgery in the 2015-2018 NSQIP database were included. Diagnosis of cancer and BMI ≥ 30 were excluded. Subjects were grouped based on positioning: reverse-Trendelenburg (RT), supine (S), and Trendelenburg (T).The RT, S, and T groups consisted of 117,887, 66,511, and 189,619 subjects, respectively. Overall median BMI was 25.7, and 82.8% of subjects were non-smokers. VTE within 30 days postoperative was seen in 0.25% RT, 0.23% S, and 0.4% T (p 0.0001); 30-day mortality was 0.34% RT, 0.25% S, and 0.19% T (p 0.0001). After adjusting for potential confounders and other risk factors, RT position was associated with a lower risk of VTE compared to S (OR 1.49 with 95% CI 1.16, 1.93) and T (OR 1.34 with 95% CI 1.15, 1.56) positions. VTE risk was significantly different across the three groups (p = 0.0001). Inpatient procedures had a higher VTE risk vs outpatient (OR 2.49 with 95% CI 2.10, 2.95). Increasing operative time was associated with higher VTE risk [4th ( 106 min) vs 1st (≤ 40 min) quartiles (OR 3.54 with 95% CI 2.79, 4.48)].Among other risk factors, inpatient procedures and longer operative times are associated with higher VTE risk in laparoscopic surgery performed for benign disease in non-obese patients. The risk was significantly different across the three positioning groups with lowest risk in the RT group and highest risk in the S group.

Cotton is the most important fiber crop and provides indispensable natural fibers for the textile industry. Micronaire (MIC) is determined by fiber fineness and maturity and is an important component of fiber quality. Gossypium barbadense L. possesses long, strong and fine fibers, while upland cotton (Gossypium hirsutum L.) is high yielding with high MIC and widely cultivated worldwide. To identify quantitative trait loci (QTLs) and candidate genes for MIC in G. barbadense, a population of 250 backcross inbred lines (BILs), developed from an interspecific cross of upland cotton CRI36 × Egyptian cotton (G. barbadense) Hai7124, was evaluated in 9 replicated field tests. Based on a high-density genetic map with 7709 genotyping-by-sequencing (GBS)-based single-nucleotide polymorphism (SNP) markers, 25 MIC QTLs were identified, including 12 previously described QTLs and 13 new QTLs. Importantly, two stable MIC QTLs (qMIC-D03-2 on D03 and qMIC-D08-1 on D08) were identified. Of a total of 338 genes identified within the two QTL regions, eight candidate genes with differential expression between TM-1 and Hai7124 were identified. Our research provides valuable information for improving MIC in cotton breeding.

The goal of this study was to correlate upright and prone bolus transit time (BTT) on barium esophagography (BE) with esophageal peristalsis on high-resolution manometry (HRM) and self-reported dysphagia in patients with normal lower esophageal sphincter parameters on HRM.BTT on BE could be the gold standard for assessing the effectiveness of esophageal peristalsis if it can be quantified.Patients with normal lower esophageal sphincter parameters and standard-protocol BE from 2017 to 2020 were included. Patients were divided, based on the number of normal swallows (distal contractile integral450 mm Hg-s-cm), into 11 groups (10 normal swallows to 0 normal swallows). Liquid barium swallows in prone position were objectively evaluated for prone BTT. Patients reported difficulty in swallowing on a scale from 0 (none) to 4 (very severe). Fractional polynomial and logistic regression analysis were used to study the association (along with the rate of change) between BTT, peristalsis, and dysphagia.A total of 146 patients were included. Prone BTT increased as the number of normal swallows decreased ( P0.001). Two deflection points were noted on the association between peristalsis and prone BTT at 50% normal swallows, 40 seconds and 30% normal swallows, 80 seconds, after which peristaltic function declined independently of prone BTT. Patients with prone BTT40 seconds had nearly 6-fold higher odds of 0% normal swallows on HRM than patients with prone BTT40 seconds ( P =0.002). Increasing prone BTT was associated with increasing dysphagia grades 1 and 2 ( P ≤0.036).Esophageal motility can be quantified by BE. Prone BTT correlates with the proportion of normal esophageal swallows and dysphagia.

BackgroundBone loss is a major public health concern with large proportions of older women experiencing osteoporotic fractures. Previous research has established a relationship between psychosocial stressors and fractures. However, few studies have investigated bone loss as an intermediary in this relationship. This study investigates whether social stress is associated with bone loss during a 6-year period in postmenopausal women.MethodsData from 11 020 postmenopausal women from the USA was used to examine self-reported psychosocial stress in relation to change in bone mineral density (BMD) measured at the femoral neck, lumbar spine and total hip. Linear regression models were used to examine associations between social measures of psychosocial stress (social strain, social functioning and social support) and per cent change in BMD over 6 years.ResultsHigh social stress was associated with decreased BMD over 6 years. After adjustment for confounders, each point higher in social strain was associated with 0.082% greater loss of femoral neck BMD, 0.108% greater loss of total hip BMD and 0.069% greater loss of lumbar spine BMD (pConclusionThe findings provide evidence for an association between high social stress and greater bone loss over 6 years of follow-up. In agreement with the prior literature, the findings for social strain and social functioning suggest that poor quality of social relationships may be associated with bone loss in postmenopausal women.

Irregular coal faces, ineluctable in coal mines within the eastern mining area in China owing to its complex geological condition, face higher rock burst danger because of their high-stress concentration and complicated spatial structure. Considering geological characteristics, rock burst liability and in situ stress in the 3303 irregular coal face at the Yangcheng coal mine, rock burst danger during tunneling and mining was analyzed to select targeted mitigation measures. The results indicate that the dynamic pressure adjustment movement (DPAM) of the roof plays an important role in the occurrence of rock bursts. Rock burst danger in tunneling of the tailgate is caused by the combination of dynamic and static stress, where the static stress is from the large depth and nearby faults, and the dynamic stress is from the DPAM of the roof above the near the 3301 mined-out area. The tunneling construction was halted for 3 months to reduce the high dynamic stress σd, and destressing large-diameter holes were drilled to reduce the static stress σ0. The rest of the tunneling construction was deemed safe. Furthermore, the rock burst danger in mining was divided into two types: I (high static stress type) and II (high dynamic stress type). The former is located at the triangular coal pillar and within a 20–150 m range ahead of the coal face. The latter acts on the tailgate caused by the intense mine seismic activity arising from the secondary DPAM. More destress holes are drilled within the danger zones of the former to release the stress fully. A combination of rigid support and flexible support (i.e., single props, double T-steel shed, bolt, anchor rope and anchor net) and monitoring is an efficient method to address the latter. The results show safe mining during the rest of the mining period. This paper provides a reference for prevention and control of rock burst for similar coal faces.

Background: Respiratory rate (RR) is a key component in commonly-used trauma scoring systems [e.g., Revised Trauma Score (RTS), TRISS]. Imprecise documentation of RR introduces misclassification when these tools are used in trauma research. By identifying each waveform, nasal cannula end tidal CO2 (NCCO2) accurately measures RR in non-intubated patients. Objective: Evaluate the relationship between EMS-documented RR measurements in patient care records (PCRs) vs. true RR recorded by non-invasive NCCO2 monitoring in major TBI patients who were never actively ventilated. Methods: Among spontaneously-breathing, major TBI cases (moderate/severe/critical), continuous NCCO2 data (Philips MRx™) were evaluated from the EPIC Prehospital TBI Study (NIH 1R01NS071049). RR classifications for RTS/TRISS were then established for each case using both PCR-documentation and monitor data. Routine monitor data (including RR) were available to EMS providers on the display at all times during care. Results: Included: 158 cases from 7 Arizona EMS agencies [(7/13-7/17; median age 55 (range 18-94); 65% male]. The Table shows RTS/TRISS case classification by PCR and monitor RR. PCR-documented RR frequently failed to correctly classify cases: RR 29: (11/34, 32.4%), normal (67/93, 72.0%; Table). In total, PCR documentation misclassified 48.7% of cases (77/158). Conclusion: These findings identify a major contributor to inaccurate trauma scoring. Since RTS and TRISS are used widely in research, this has important implications for study enrollment, case ascertainment, confounding, and risk-adjustment in injury studies. Whenever possible, QI and research studies should utilize monitor data to identify and evaluate RR and other vitals rather than relying on PCR documentation. Future development of monitor-based, real-time feedback technology might improve trauma scoring precision and provider identification of RR abnormalities.

Background: Recent studies have shown that prehospital systolic blood pressure (SBP) is strongly associated with mortality across a remarkably wide range (far above 90 mmHg) in traumatic brain injury (TBI). Furthermore, in TBI research, trial enrollment and risk-adjustment are highly dependent upon accurate documentation of BP. Our preliminary work identified potential discrepancies between EMS-documented vs. actual measured BP. Objective: In major TBI, evaluate concordance between SBP documented in EMS patient care records (PCR) and actual, monitor-recorded SBP. Methods: A subset of major TBI cases (mod/severe/critical) in the EPIC TBI Study (NIH 1R01NS071049) were analyzed (3/13-7/18). Cases from 6 EMS agencies reporting continuous monitor data (Philips MRx™) were included. All monitor data available for this analysis were displayed and accessible to the providers during EMS care. We compared the lowest PCR-documented SBP to the monitor-recorded value in each patient. Results: Included: 210 cases (median age: 52, 67% male). In 152 cases (72%), the lowest PCR-documented SBP was exactly concordant with the monitor. When concordance was defined by a difference of ≤5 mmHg, 171 (81%) were concordant. Among the 27 cases with monitor-identified hypotension ( Conclusions: Significant disparities existed between monitor-recorded and PCR-documented SBP. PCRs failed to reflect 33% of monitor-documented hypotensive cases. It appears that ongoing care responsibilities and scene distractions may cause providers to miss important BP readings. These findings identify a potential hidden contributor to poor outcomes if hypotension goes unrecognized and untreated, rather than simply not being documented. Furthermore, case ascertainment, trial enrollment, confounding, and risk-adjustment in TBI studies may be substantially impacted when these processes are based on EMS documentation. When possible, QI and research projects should utilize monitor data to identify hypotensive patients. Development of real-time audiovisual monitor feedback technology might improve provider recognition of hypotension.

Introduction: The Prehospital TBI Guidelines (PTGs) are intended for both isolated and multisystem TBI (ITBI/MTBI). However, uncontrolled hemorrhage and potential detrimental effects of fluid resuscitation in MTBI may lead to differential effectiveness compared to ITBI. Methods: Preplanned subgroup analysis of PTG effectiveness in ITBI and MTBI from EPIC (before/after system study; 133 agencies, >11,000 trained; NIH R01NS071049). Interventions: Prevention/treatment of hypoxia, hypotension, hyperventilation. Inclusion: Barell Matrix 1; 1/07-6/15. Severity subgroups [Head Region Severity Score (HRSS; AIS equivalent)]: Moderate = 1-2; Severe = 3-4; Critical = 5-6. Definitions: ITBI: TBI with no other RSS ≥3 injury. MTBI: TBI plus non-head region RSS ≥3 injuries. Pre (P1) and post-implementation (P3) cohorts were compared using logistic regression. Results: Cases: 21,852; median age 45 (IQR 24, 66); 67% male. ITBI: 16,663 (76.3%); P1 = 11,602, P3 = 5061. MTBI: 5189 (23.7%); P1 = 3626, P3 = 1563]. Hypotension occurred much more frequently in MTBI (15.8%) than ITBI (4.5%; OR = 3.9 (3.5, 4.4); p Conclusions: PTG implementation was independently associated with improved odds of survival in severe ITBI and MTBI. Despite a rate of hypotension 4 times higher in MTBI, survival improvement was at least as strong as for ITBI. Since the MTBI cohort was much more likely to receive fluid resuscitation, these findings support the PTG recommendation for aggressive treatment of hypotension in TBI even in patients with potential ongoing hemorrhage.

OBJECTIVE: To evaluate serum concentrations of polyfluoroalkyl substances (PFAS) in male firefighters and association with cardiometabolic markers. METHODS: Serum PFAS were evaluated in 38 Arizona firefighters and 49 participants from the 2009–2010 National Health and Nutrition Examination Survey (NHANES). Cardiometabolic markers including carotid intima-medial thickness (CIMT) were measured in the firefighters. RESULTS: Firefighters had elevated perfluorohexane sulfonic acid (PFHxS) and lower perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) compared to NHANES participants; for nine of the other 12 PFAS the values were not significantly different. There were significant negative associations among firefighters between perfluorodecanoic acid (PFDeA) and total cholesterol and PFUA and interleukin-6. PFAS concentrations were not associated with CIMT. CONCLUSION: PFHxS levels were elevated and PFNA and PFUA levels were decreased in firefighters compared to NHANES subjects. Serum PFAS concentrations were not associated with increased cardiometabolic risk measures in this population of firefighters.

BACKGROUND Exosomes isolated from plasma of lung transplant recipients (LTxRs) with bronchiolitis obliterans syndrome (BOS) contain human leukocyte antigens and lung self-antigens (SAgs), K-alpha 1 tubulin (Kα1T) and collagen type V (Col-V). The aim was to determine the use of circulating exosomes with lung SAgs as a biomarker for BOS. METHODS Circulating exosomes were isolated retrospectively from plasma from LTxRs at diagnosis of BOS and at 6 and 12 months before the diagnosis (n = 41) and from stable time-matched controls (n = 30) at 2 transplant centers by ultracentrifugation. Exosomes were validated using Nanosight, and lung SAgs (Kα1T and Col-V) were detected by immunoblot and semiquantitated using ImageJ software. RESULTS Circulating exosomes from BOS and stable LTxRs demonstrated 61- to 181-nm vesicles with markers Alix and CD9. Exosomes from LTxRs with BOS (n = 21) showed increased levels of lung SAgs compared with stable (n = 10). A validation study using 2 separate cohorts of LTxRs with BOS and stable time-matched controls from 2 centers also demonstrated significantly increased lung SAgs–containing exosomes at 6 and 12 months before BOS. CONCLUSIONS Circulating exosomes isolated from LTxRs with BOS demonstrated increased levels of lung SAgs (Kα1T and Col-V) 12 months before the diagnosis (100% specificity and 90% sensitivity), indicating that circulating exosomes with lung SAgs can be used as a non-invasive biomarker for identifying LTxRs at risk for BOS.

Study Objective To investigate the impact of retained cystoscopy fluid after laparoscopic hysterectomy on time to spontaneous void, time to discharge, urinary retention, bladder discomfort, and patient satisfaction. Design Single-blind randomized controlled trial. Setting An academic medical center. Patients One hundred and twenty patients who underwent laparoscopic hysterectomy with universal cystoscopy for benign indications, excluding pelvic organ prolapse and urinary incontinence indications. Interventions From October 10, 2018, to October 17, 2019, we compared 200 mL retained cystoscopy fluid and complete bladder emptying after laparoscopic hysterectomy with universal cystoscopy. Measurements and Main Results A total of 120 patients were enrolled and randomized (59 in the retained cystoscopy fluid group and 61 in the emptied fluid group). The primary outcome was time to first spontaneous void. The secondary outcomes were time to discharge, urinary retention rates, bladder discomfort, and patient satisfaction. A sample size of 120 was calculated to detect a 57-minute difference in time to spontaneous void. There were minimal differences in baseline demographics and surgical characteristics between the groups. There was an apparent, although not significant, difference in time to void of 25 minutes (143 minutes vs 168 minutes, p = .20). Time to discharge and urinary retention rates did not differ (199 minutes vs 214 minutes, p = .40, and 13.6% vs 8.2%, p = .51, respectively). There was no difference in postoperative bladder discomfort and patient satisfaction. Conclusion Retained cystoscopy fluid after laparoscopic hysterectomy did not significantly affect time to first spontaneous void, time to discharge, urinary retention, bladder discomfort, or patient satisfaction.

Women approximate one-third of the annual 2.8 million people in the United States who sustain traumatic brain injury (TBI). Several clinical reports support or refute that menstrual cycle-dependent fluctuations in sex hormones are associated with severity of persisting post-TBI symptoms. Previously, we reported late-onset sensory hypersensitivity to whisker stimulation that corresponded with changes in glutamate neurotransmission at 1-month following diffuse TBI in male rats. Here, we incorporated intact age-matched naturally cycling females into the experimental design while monitoring daily estrous cycle. We hypothesized that sex would not influence late-onset sensory hypersensitivity and associated in vivo amperometric extracellular recordings of glutamate neurotransmission within the behaviorally relevant thalamocortical circuit. At 28 days following midline fluid percussion injury (FPI) or sham surgery, young adult Sprague-Dawley rats were tested for hypersensitivity to whisker stimulation using the whisker nuisance task (WNT). As predicted, both male and female rats showed significantly increased sensory hypersensitivity to whisker stimulation after FPI, with females having an overall decrease in whisker nuisance scores (sex effect), but no injury and sex interaction. In males, FPI increased potassium chloride (KCl)-evoked glutamate overflow in primary somatosensory barrel cortex (S1BF) and ventral posteromedial nucleus of the thalamus (VPM), while in females the FPI effect was discernible only within the VPM. Similar to our previous report, we found the glutamate clearance parameters were not influenced by FPI, while a sex-specific effect was evident with female rats showing a lower uptake rate constant both in S1BF and VPM and longer clearance time (in S1BF) in comparison to male rats. Fluctuations in estrous cycle were evident among brain-injured females with longer diestrus (low circulating hormone) phase of the cycle over 28 days post-TBI. Together, these findings add to growing evidence indicating both similarities and differences between sexes in a chronic response to TBI. A better understanding of the influence of gonadal hormones on behavior, neurotransmission, secondary injury and repair processes after TBI is needed both clinically and translationally, with potential impact on acute treatment, rehabilitation, and symptom management.

Study objective We evaluate the effect of implementing the out-of-hospital pediatric traumatic brain injury guidelines on outcomes in children with major traumatic brain injury. Methods The Excellence in Prehospital Injury Care for Children study is the preplanned secondary analysis of the Excellence in Prehospital Injury Care study, a multisystem, intention-to-treat study using a before-after controlled design. This subanalysis included children younger than 18 years who were transported to Level I trauma centers by participating out-of-hospital agencies between January 1, 2007, and June 30, 2015, throughout Arizona. The primary and secondary outcomes were survival to hospital discharge or admission for children with major traumatic brain injury and in 3 subgroups, defined a priori as those with moderate, severe, and critical traumatic brain injury. Outcomes in the preimplementation and postimplementation cohorts were compared with logistic regression, adjusting for risk factors and confounders. Results There were 2,801 subjects, 2,041 in preimplementation and 760 in postimplementation. The primary analysis (postimplementation versus preimplementation) yielded an adjusted odds ratio of 1.16 (95% confidence interval 0.70 to 1.92) for survival to hospital discharge and 2.41 (95% confidence interval 1.17 to 5.21) for survival to hospital admission. In the severe traumatic brain injury cohort (Regional Severity Score–Head 3 or 4), but not the moderate or critical subgroups, survival to discharge significantly improved after guideline implementation (adjusted odds ratio = 8.42; 95% confidence interval 1.01 to 100+). The improvement in survival to discharge among patients with severe traumatic brain injury who received positive-pressure ventilation did not reach significance (adjusted odds ratio = 9.13; 95% confidence interval 0.79 to 100+). Conclusion Implementation of the pediatric out-of-hospital traumatic brain injury guidelines was not associated with improved survival when the entire spectrum of severity was analyzed as a whole (moderate, severe, and critical). However, both adjusted survival to hospital admission and discharge improved in children with severe traumatic brain injury, indicating a potential severity-based interventional opportunity for guideline effectiveness. These findings support the widespread implementation of the out-of-hospital pediatric traumatic brain injury guidelines.